α-substituted phenylacetic acid derivative, its production and agricultural fungicide containing it

ABSTRACT

An α-substituted phenylacetic acid derivative useful as an agricultural fungicide, represented by general formula (I), or a salt thereof, a process for producing the same, an intermediate for the production thereof, and an agricultural fungicide containing the same as the active ingredient, wherein R 1  represents halogen, alkyl, OH, alkylthio, alkylsulfinyl, alkylsulfonyl, amino or nitro; Q represents aryl, heterocycle, mono- or disubstituted methyleneamino, (substituted amino-)methyl, alkyl, alkenyl, alkynyl, substituted carbonyl or substituted sulfonyl; X represents hydrogen, halogen, alkyl or OH; Y represents OH, alkylthio or amino; Z represents oxygen or sulfur; M represents oxygen, S(O)i (i being 0, 1 or 2), NR 2  (R 2  being hydrogen, alkyl or acyl) or a single bond; and n represents 0, 1 or 2. ##STR1##

TECHNICAL FIELD

The present invention relates to a novel α-substituted phenylacetic acid derivative, a process for producing it, and an agricultural fungicide containing it as an active ingredient.

BACKGROUND OF THE INVENTION

Certain kinds of α-substituted phenyl acetic acid ester derivatives have been disclosed in JP-A 60-54949 and DE2742065. However, each of these compounds has a substituent at the 3-position of the phenyl group, and no compounds having a substituent at the 2-position have been disclosed. JP-A 3-17052 and JP-A 3-157350 also disclose α-substituted phenylacetic acid ester derivatives. However, they only disclose 2-hydroxy-2-phenylacetic acid or its acetic acid ester as an intermediate or insecticide, and do not disclose its fungicidal activity at all.

JP-A 4-288045, JP-A 4-261147, WO93/15046, EP-A-498396, JP-A 3-169842, EP-A-532022, JP-A 7-17930, and EP-A-619301 also disclose related compounds.

The present invention is to provide a novel compound having potent fungicidal activity, a process for producing it, and an agricultural fungicide containing it as an active ingredient.

DISCLOSURE OF THE INVENTION

Under these circumstances, the present inventors have intensively studied to obtain compounds having potent fungicidal activity. As a result, it has been found that a novel α-substituted phenylacetic acid derivative having a substituent at the 2-position in the phenyl group has potent fungicidal activity. Thus, the present invention has been completed.

The present invention provides:

1. A compound of the formula (I): ##STR2## wherein R¹ is a halogen atom, optionally substituted alkyl, optionally substituted hydroxyl, alkylthio, alkylsulfinyl, alkylsulfonyl, optionally substituted amino or nitro; Q is optionally substituted aryl, an optionally substituted heterocyclic group, mono- or di-substituted methyleneamino, optionally substituted (substituted imino)methyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, substituted carbonyl or substituted sulfonyl; X is a hydrogen atom, halogen atom, optionally substituted alkyl or optionally substituted hydroxyl; Y is optionally substituted hydroxyl, alkylthio or optionally substituted amino, provided that, when R¹ is hydroxyl, Y is not alkoxy; Z is an oxygen atom or sulfur atom; M is an oxygen atom, S(O)_(i) (in which i is 0, 1 or 2), NR² (in which R² is a hydrogen atom, alkyl or acyl) or a single bond; and n is 0, 1 or 2; or a salt thereof;

2. A compound according to the above item 1, wherein R¹ is a halogen atom, alkyl, haloalkyl, alkoxyalkyl, hydroxyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, haloalkenyloxy, haloalkynyloxy, alkoxyalkoxy, alkylcarbonyloxy, (alkylthio)carbonyloxy, alkylsulfonyloxy, arylsulfonyloxy, mono-or di-alkyl-substituted carbamoyloxy, aryloxy, alkylthio, alkylsulfinyl, alkylsulfonyl, amino optionally substituted by alkyl, nitro or tetrahydropyranyloxy, or a salt thereof;

3. A compound according to the above item 1, wherein R¹ is alkoxy, or a salt thereof;

4. A compound according to the above item 1, wherein R¹ is methoxy, or a salt thereof;

5. A compound according to the above item 1, wherein Q is a group of the formula (XX): ##STR3## wherein U, V and W are the same or different and are a hydrogen atom, halogen atom, optionally substituted alkyl, optionally substituted hydroxyl, alkylthio or optionally substituted amino, or a salt thereof;

6. A compound according to the above item 5, wherein U, V and W are the same or different and are a hydrogen, chlorine atom, methyl, trifluoromethyl or methoxy, or a salt thereof;

7. A compound according to the above item 1, wherein Q is pyridyl, pyrimidinyl, quinolyl, quinazolinyl, benzothiazolyl or pyrazolyl, each of which may be substituted, or a salt thereof;

8. A compound according to the above item 1, wherein Q is optionally substituted pyridyl, or a salt thereof;

9. A compound according to the above item 1, wherein Q is a group of the formula (a): ##STR4## wherein R¹² and R¹³ are the same or different and are a hydrogen atom, optionally substituted alkyl, acyl, alkylthio, alkylsulfinyl, alkylsulfonyl, optionally substituted amino, cycloalkyl, optionally substituted aryl or an optionally substituted heterocyclic group, or R¹² and R¹³ are linked together to form a monocyclic or polycyclic ring which may contain a heteroatom, or a salt thereof;

10. A compound according to the above item 9, wherein R¹² and R¹³ are the same or different and are a hydrogen atom, alkyl, haloalkyl, alkoxyalkyl, alkylcarbonyl, optionally substituted phenyl, optionally substituted naphthyl or an optionally substituted heterocyclic group, or R¹² and R¹³ are linked together to form a cyclopentane ring or cyclohexane ring each of which may form a condensed ring with another ring, or a salt thereof;

11. A compound according to the above item 9, wherein R¹² is alkyl, or a salt thereof;

12. A compound according to the above item 9, wherein R¹² is methyl or ethyl, or a salt thereof;

13. A compound according to the above item 9, wherein R¹³ is phenyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, optionally substituted alkyl, optionally substituted hydroxyl, alkylthio, optionally substituted amino, nitro, phenyl and cyano, or a salt thereof;

14. A compound according to the above item 9, wherein R¹³ is phenyl optionally substituted by 1 to 3 substituents selected from the group consisting of a chlorine atom, methyl, trifluoromethyl and methoxy, or a salt thereof;

15. A compound according to the above item 9, wherein R¹³ is pyridyl, pyridazinyl, pyrazolyl, pyrimidinyl, furyl, thienyl, oxazolyl, isoxazolyl, benzothiazolyl, quinolyl, quinazolinyl, pyrazinyl, morpholino or piperazinyl, each of which may substituted, or a salt thereof;

16. A compound according to the above item 1, wherein X is a hydrogen atom, or a salt thereof;

17. A compound according to the above item 1, wherein Y is alkoxy, or a salt thereof;

18. A compound according to the above item 1, wherein Y is methoxy, or a salt thereof;

19. A compound according to the above item 1, wherein Y is monoalkylamino, or a salt thereof;

20. A compound according to the above item 1, wherein Y is monomethylamino, or a salt thereof;

21. A compound according to the above item 1, wherein Z is an oxygen atom, or a salt thereof;

22. A compound according to the above item 1, wherein M is an oxygen atom, sulfur atom or optionally substituted amino, or a salt thereof;

23. A compound according to the above item 1, wherein n is 0, or a salt thereof;

24. A compound according to the above item 1, wherein n is 1, or a salt thereof;

25. An agricultural fungicidal composition comprising a compound according to the above item 1 as an active ingredient;

26. A process for producing a compound of the formula (I-1): ##STR5## wherein each symbol is as defined in the above item 1, which comprises reducing a compound of the formula (II): ##STR6## wherein each symbol is as defined in the above 1;

27. A process for producing a compound of the formula (I-2): ##STR7## wherein R³ is alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, alkylcarbonyl, (alkylthio)carbonyl, alkylsulfonyl, arylsulfonyl, or mono- or di-alkyl-substituted carbamoyl, and the other symbols are as defined in the above item 1, which comprises reacting a compound of the formula (I-1): ##STR8## wherein each symbol is as defined in the above item 1, with a compound of the formula (XXII):

    R.sup.3 --L                                                (XXII)

wherein L is a leaving group, and the other symbols are as defined above;

28. A process for producing a compound of the formula (IV-2): ##STR9## wherein R⁴ is alkyl, alkenyl, alkynyl, haloalkyl or alkoxyalkyl, R⁵ is a hydrogen atom or alkyl, R⁶ is a hydrogen atom, alkyl or hydroxylalkyl, and the other symbols are as defined in the above item 1, which comprises reacting a compound of the formula (IV-1): ##STR10## wherein Y¹ is alkoxy or alkylthio and the other symbols are as defined above, with an amine;

29. A process for producing a compound of the formula (I-5): ##STR11## wherein A is a halogen atom, and the other symbols are as defined in the above item 1, which comprises halogenating a compound of the formula (I-1): ##STR12## wherein each symbol is as defined in the above item 1;

30. A process for producing a compound of the formula (I-6): ##STR13## wherein B is alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, alkoxyalkoxy, alkylthio, amino optionally substituted by alkyl, or nitro, and the other symbols are as defined in the above item 1, which comprises reacting a compound of the formula (I-5): ##STR14## wherein A is a halogen atom and the other symbols are as defined in the above item 1, with a nucleophile;

31. A process for producing a compound of the formula (I): ##STR15## wherein each symbol is as defined in the above 1, which comprises reacting a compound of the formula (XVIII): ##STR16## wherein D is a halogen atom, and the other symbols are as defined in the above item 1, with a compound of the formula (XIX):

    Q--MH                                                      (XIX)

wherein each symbol is as defined in the above item 1;

32. A process for producing a compound of the formula (I): ##STR17## wherein each symbol is as defined in the above item 1, which comprises reacting a compound of the formula (XXIII): ##STR18## wherein each symbol is as defined in the above item 1, with a compound of the formula (XXIV):

    Q--L                                                       (XXIV)

wherein L is a leaving group, and Q is as defined in the above item 1;

33. A compound of the formula (XXXIX): ##STR19## wherein R⁵ is a hydrogen atom or alkyl, R⁶ is a hydrogen atom, alkyl or hydroxylalkyl, R¹⁰ is optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl, D is a halogen atom, and the other symbols are as defined in the above item 1, or a salt thereof;

34. A compound of the formula (XXXII): ##STR20## wherein Y² is alkoxy, E is a protected hydroxyl, and the other symbols are as defined in the above item 1, or a salt thereof;

35. A compound according to the above item 34, wherein E is tetrahydropyranyloxy or 1-ethoxyethoxy, or a salt thereof;

36. A compound of the formula (XXXV): ##STR21## wherein R¹⁰ is optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl, Y² is alkoxy, E is a protected hydroxyl, and the other symbols are as defined in the above item 1, or a salt thereof;

37. A compound according to the above item 36, wherein E is tetrahydropyranyloxy or 1-ethoxyethoxy, or a salt thereof;

38. A compound of the formula (XXXVI): ##STR22## wherein R¹⁰ is optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl, and the other symbols are as defined in the above item 1, or a salt thereof;

39. A compound of the formula (XXXVII): ##STR23## wherein R⁵ is a hydrogen atom or alkyl, R⁶ is a hydrogen atom, alkyl or hydroxylalkyl, R¹⁰ is optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl, and the other symbols are as defined in the above item 1, or a salt thereof; and

40. A compound according to any one of the above items 33 to 39, wherein Z is an oxygen atom, or a salt thereof.

The halogen atom represented by R¹ includes fluorine, chlorine, bromine and iodine.

The optionally substituted alkyl represented by R¹ includes, for example, alkyl having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, etc. In particular, methyl and ethyl are preferred. The substituted alkyl includes, for example, haloalkyl having as a substituent at least one halogen atom (e.g., fluorine, chlorine, bromine, iodine, preferably fluorine)(e.g., difluoromethyl, trifluoromethyl, chloromethyl, 2-bromoethyl, 2,3-dichloropropyl, etc.); alkoxyalkyl having as a substituent alkoxy having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms (e.g., methoxy, ethoxy, propoxy, butoxy, etc.)(e.g., methoxymethyl, ethoxymethyl, methoxyethyl, etc.), etc. In particular, trifluoromethyl is preferred for the haloalkyl, and methoxymethyl is preferred for the alkoxyalkyl.

The optionally substituted hydroxyl represented by R¹ includes, for example, hydroxyl, optionally substituted alkoxy, optionally substituted alkenyloxy, optionally substituted alkynyloxy, alkylcarbonyloxy, (alkylthio)carbonyloxy, alkylsulfonyloxy, arylsulfonyloxy, mono- or di-alkyl-substituted carbamoyloxy, aryloxy, tetrahydropyranyloxy, etc.

Examples of the optionally substituted alkoxy include alkoxy having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, t-butoxy, pentyloxy, hexyloxy, etc.: haloalkoxy having as a substituent at least one halogen atom (e.g., fluorine, chlorine, bromine, iodine, preferably fluorine) such as difluoromethoxy, trifluoromethoxy, chloromethoxy, etc.; alkoxyalkoxy having as a substituent alkoxy having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms (e.g., methoxy, ethoxy, propoxy, butoxy, etc.) such as methoxymethoxy, 2-methoxyethoxy, ethoxymethoxy, etc. Methoxy, ethoxy and butoxy, in particular methoxy, are preferred for the alkoxy. Difluoromethoxy is preferred for the haloalkoxy. Methoxymethoxy is preferred for the alkoxyalkoxy.

Examples of the optionally substituted alkenyloxy include alkenyloxy having 2 to 8 carbon atoms, preferably 2 to 4 carbon atoms, such as vinyloxy, allyloxy, propenyloxy, isopropenyloxy, butenyloxy, isobutenyloxy, pentenyloxy, hexenyloxy, hexadienyloxy, etc.; haloalkenyloxy having as a substituent at least one halogen atom (e.g., fluorine, chlorine, bromine, iodine) such as 3,3-dichloro-2-propenyloxy, 4,4,4-trifluoromethyl-2-butenyloxy, etc. In particular, allyloxy is preferred.

Examples of the optionally substituted alkynyloxy include alkynyloxy having 2 to 8 carbon atoms, preferably 2 to 4 carbon atoms, such as ethynyloxy, propargyloxy, butynyloxy, etc.; haloalkynyloxy having as a substituent at least one halogen atom (e.g., fluorine, chlorine, bromine, iodine) such as 3-chloro-2-propynyloxy, 4,4,4-trifluoromethyl-2-butynyloxy, etc. In particular, propargyloxy is preferred.

Examples of the alkylcarbonyloxy include alkylcarbonyloxy which contains alkyl having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms, such as acetoxy, propionyloxy, butyryloxy, etc. In particular, acetoxy is preferred.

Examples of the (alkylthio)carbonyloxy include (alkylthio)carbonyloxy which contains alkyl having 1 to 8 carbon atom, preferably 1 to 4 carbon atoms, such as (methylthio)carbonyloxy, (ethylthio)carbonyloxy, (propylthio)carbonyloxy, etc. In particular, (methylthio)carbonyloxy is preferred.

Examples of the alkylsulfonyloxy include alkylsulfonyloxy which contains alkyl having 1 to 8 carbon atom, preferably 1 to 4 carbon atom, such as methanesulfonyloxy, ethanesulfonyloxy, propanesulfonyloxy, etc. In particular, methanesulfonyloxy is preferred.

Examples of the arylsulfonyloxy include arylsulfonyloxy which contains aryl having 6 to 12, preferably 6 to 8 carbon atoms, such as benzenesulfonyloxy, p-toluenesulfonyloxy, etc. In particular, p-toluenesulfonyoxy is preferred.

Examples of the mono- or di-alkyl-substituted carbamoyloxy include mono- or di-alkyl-substituted carbamoyloxy which contains alkyl having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms, such as N-monomethylcarbamoyloxy, N,N-dimethylcarbamoyloxy, N-monoethylcarbamoyloxy, etc. In particular, N,N-dimethylcarbamoyloxy is preferred.

Examples of the aryloxy include aryloxy having 6 to 12, preferably 6 to 8 carbon atoms, such as phenoxy, 2-methyl-phenoxy, 2,5-dimethylphenoxy, etc.

Examples of the tetrahydropyranyloxy include 2-tetrahydropyranyloxy, etc.

The alkylthio represented by R¹ includes, for example, alkylthio having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms, such as methylthio, ethylthio, propylthio, and butylthio. In particular, methylthio is preferred.

The alkylsulfinyl represented by R¹ includes, for example, alkylsulfinyl having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms, such as methylsulfinyl, ethylsulfinyl, propylsulfinyl, etc. In particular, methylsulfinyl is preferred.

The alkylsulfonyl represented by R¹ includes, for example, alkylsulfonyl having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms, such as methylsulfonyl, ethylsulfonyl, propylsulfonyl, etc. In particular, methylsulfonyl is preferred.

The optionally substituted amino represented by R¹ includes, for example, amino, amino mono- or di-substituted by alkyl having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms (e.g., monomethylamino, dimethylamino, monoethylamino, etc.), amino mono-substituted by formyl, amino mono-substituted by alkylcarbonyl having 2 to 8 carbon atoms, preferably 2 to 4 carbon atom (e.g., methylcarbonylamino, etc.), etc. Amino substituted by alkyl having 1 to 4 carbon atoms is preferred. In particular, monomethylamino is preferred.

R¹ is preferably a halogen atom, alkyl, haloalkyl, alkoxyalkyl, hydroxyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, haloalkenyloxy, haloalkynyloxy, alkoxyalkoxy, alkylcarbonyloxy, (alkylthio)carbonyloxy, alkylsulfonyloxy, arylsulfonyloxy, mono- or di-alkyl-substituted carbamoyloxy, aryloxy, alkylthio, alkylsulfinyl, alkylsulfonyl, amino optionally substituted by alkyl, nitro, or tetrahydropyranyloxy. Alkoxy or hydroxy is more preferred. In particular, methoxy is preferred.

The optionally substituted aryl represented by Q includes, for example, aryl having 6 to 14 carbon atoms such as phenyl, naphthyl, etc. When the aryl is substituted, the substituent is selected from lower alkyl (wherein "lower" means C₁₋₈, preferably C₁₋₆, more preferably C₁₋₄ ; "lower" has the same meaning in other substituents described below) (e.g., methyl, ethyl, propyl, butyl, etc.), lower alkenyl (e.g., vinyl, allyl, crotyl, etc.), lower alkynyl (e.g., ethynyl, propargyl, butynyl, etc.), cycloalkyl (e.g., cyclopropyl, cyclopentyl, cyclohexyl, etc.), lower alkoxy lower alkyl (e.g., methoxymethyl, ethoxymethyl, 2-methoxyethyl, etc.), cycloalkenyl (e.g., cyclopentenyl, cyclohexenyl, etc.), lower alkanoyl (e.g., acetyl, propionyl, isobutyryl, etc.), lower alkylsilyl (e.g., trimethylsilyl, triethylsilyl, tripropylsilyl, tributylsilyl, etc.), halo(lower)alkyl (e.g., difluoromethyl, trifluoromethyl, chloromethyl, 2-bromoethyl, 2,3-dichloropropyl, etc.), di(lower)alkylamino (e.g., dimethylamino, diethylamino, etc.), phenyl, phenyl(lower)alkyl (e.g., benzyl, phenethyl, etc.), phenyl(lower)alkenyl (e.g., styryl, cinnamyl, etc.), furyl(lower)alkyl (e.g., 3-furylmethyl, 2-furylethyl, etc.), furyl(lower)alkenyl (e.g., 3-furylvinyl, 2-furylallyl, etc.), a halogen atom (e.g., fluorine, chlorine, bromine, iodine), nitro, cyano, lower alkylthio (e.g., methylthio, ethylthio, propylthio, etc.), lower alkoxycarbonyl (e.g., methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, etc.), formyl, amino, mono(lower)alkylamino (e.g., methylamino, ethylamino, etc.), --OR wherein R is a hydrogen atom, lower alkyl (e.g., methyl, ethyl, propyl, butyl, etc.), lower alkenyl (e.g., vinyl, allyl, crotyl, etc.), lower alkynyl (e.g., ethynyl, 2-propynyl, 3-butynyl, etc.), halo(lower)alkyl (e.g., difluoromethyl, trifluoromethyl, chloromethyl, 2-bromoethyl, 2,3-dichloropropyl, etc.), lower alkanoyl (e.g., acetyl, propionyl, butyryl, etc.), phenyl, lower alkoxyphenyl (e.g., 3-methoxyphenyl, 4-ethoxyphenyl, etc.), nitrophenyl (e.g., 3-nitrophenyl, 4-nitrophenyl, etc.), phenyl(lower)alkyl (e.g., benzyl, phenethyl, phenylpropyl, etc.), cyanophenyl(lower)alkyl (e.g., 3-cyanophenylmethyl, 4-cyanophenylethyl, etc.), benzoyl, tetrahydropyranyl, pyridyl, trifluoromethylpyridyl, pyrimidinyl, benzothiazolyl, quinolyl, benzoyl(lower)alkyl (e.g., benzoylmethyl, benzoylethyl, etc.), benzenesulfonyl, or lower alkylbenzenesulfonyl (e.g., toluenesulfonyl, etc.)!, --CH₂ --G--R' (wherein G is --O--, --S--, or --NR"-- (in which R" is a hydrogen atom or lower alkyl), R' is phenyl, halophenyl (e.g., 2-chlorophenyl, 4-fluorophenyl, etc.), lower alkoxyphenyl (e.g., 2-methoxyphenyl, 4-ethoxyphenyl, etc.), pyridyl, or pyrimidinyl!, etc.

The substituent may be at any possible position in the ring. The number of the substituent(s) is 1 to 5, preferably 1 to 4, more preferably 1 to 3, and the substituents are the same or different.

Preferably, the optionally substituted aryl represented by Q is represented by the formula (XX): ##STR24## wherein U, V and W are the same or different and are a hydrogen atom, halogen atom, optionally substituted alkyl, optionally substituted hydroxyl, alkylthio, or optionally substituted amino.

The halogen atom represented by U, V and W includes, for example, fluorine, chlorine, bromine, and iodine. In particular, chlorine is preferred.

The optionally substituted alkyl represented by U. V and W includes, for example, the above optionally substituted alkyl represented by R¹. The optionally substituted alkyl is preferably alkyl, haloalkyl or alkoxyalkyl, more preferably methyl, ethyl or trifluoromethyl, particularly preferably methyl.

The optionally substituted hydroxyl represented by U, V and W includes, for example, the above optionally substituted hydroxyl represented by R¹. The optionally substituted hydroxyl is preferably alkoxy, alkenyloxy, alkynyloxy, haloalkoxy or phenoxy, more preferably alkoxy, particularly preferably methoxy.

The alkylthio and optionally substituted amino represented by U, V and W include the above alkylthio and optionally substituted amino represented by R¹, respectively. In particular, they are preferably methylthio and dimethylamino, respectively.

The optionally substituted heterocyclic group represented by Q is, for example, a 5- to 7-membered heterocyclic group containing as a ring-constituting atom 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur. The heterocyclic group may form a condensed ring with another heterocyclic ring or a benzene ring. Examples of the heterocyclic group include pyridyl (e.g., pyridin-2-yl, pyridin-3-yl, etc), pyrimidinyl (e.g., pyrimidin-4-yl, pyrimidin-2-yl), quinolyl (e.g., quinolin-4-yl), quinazolinyl (e.g., quinazolin-4-yl), benzothiazolyl (e.g., benzothiazol-2-yl), pyrazolyl (e.g., pyrazol-5-yl), etc., each of which is optionally substituted. In particular, optionally substituted pyridyl is preferred.

When the heterocyclic group is substituted, the substituent includes, for example, the above substituents of the aryl represented by Q. The substituent is preferably a halogen atom, halo(lower)alkyl, alkoxy, alkoxycarbonyl or formyl, more preferably a chlorine atom or trifluoromethyl. The substituent may be at any possible position in the ring. The number of the substituent(s) is 1 to 5, preferably 1 to 4, more preferably 1 to 3. The substituents are the same or different.

The mono- or di-substituted methyleneamino represented by Q is represented, for example, by the formula (a): ##STR25## wherein R¹² and R¹³ are the same or different and are a hydrogen atom, optionally substituted alkyl; acyl, alkylthio, alkylsulfinyl, alkylsulfonyl, optionally substituted amino, cycloalkyl, optionally substituted aryl or an optionally substituted heterocyclic group, or R¹² and R¹³ are linked together to form a monocyclic or polycyclic ring which may contain a heteroatom, provided that at least one of R¹² and R¹³ is not a hydrogen atom.

The alkyl represented by R¹² or R¹³ in the formula (a) includes, for example, the alkyl or substituted alkyl represented by R¹. In particular, methyl and ethyl are preferred.

The acyl represented by R¹² or R¹³ includes, for example, alkylcarbonyl, arylcarbonyl, etc. The alkylcarbonyl includes, for example, C₁₋₆ alkyl-carbonyl, preferably C₁₋₄ alkyl-carbonyl, such as acetyl, trifluoroacetyl, propionyl, butyryl, etc. The arylcarbonyl includes, for example, C₆₋₁₄ aryl-carbonyl such as benzoyl, naphthoyl, etc.

The alkylthio, alkylsulfinyl, alkylsulfonyl and optionally substituted amino represented by R¹² or R¹³ are, for example, the alkylthio, alkylsulfinyl, alkylsulfonyl and optionally substituted amino represented by R¹, respectively.

The cycloalkyl represented by R¹² or R¹³ includes cycloalkyl having 3 to 7 carbon atoms, preferably 5 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, etc.

The optionally substituted aryl represented by R¹² or R¹³ includes, for example, C₆₋₁₄ aryl such as phenyl, naphthyl (e.g., 1-naphthyl, etc.), fluorenyl, etc. In particular, phenyl is preferred. The aryl may be substituted at any possible position in the ring. The number of the substituent(s) is 1 to 3. Examples of the substituent include halogen atoms, optionally substituted alkyl, optionally substituted hydroxyl, alkylthio, optionally substituted amino, nitro, phenyl, cyano, etc.

Examples of the halogen atom as the substituent of the optionally substituted aryl represented by R¹² or R¹³ include fluorine, chlorine, bromine, and iodine.

Examples of the optionally substituted alkyl as the substituent of the optionally substituted aryl represented by R¹² or R¹³ include the above optionally substituted alkyl represented by R¹. The optionally substituted alkyl is preferably alkyl or haloalkyl, particularly preferably methyl or trifluoromethyl.

Examples of the optionally substituted hydroxyl as the substituent of the optionally substituted aryl represented by R¹² or R¹³ include hydroxyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, aryloxy, etc. The alkoxy includes, for example, alkoxy having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms, such as methoxy, ethoxy, propoxy, butoxy, etc. In particular, methoxy is preferred. The alkenyloxy includes, for example, alkenyloxy having 2 to 8 carbon atoms, preferably 2 to 4 carbon atoms, such as vinyloxy, allyloxy, crotyloxy, etc. In particular, allyloxy is preferred. The alkynyloxy includes, for example, alkynyloxy having 2 to 8 carbon atoms, preferably 2 to 4 carbon atoms, such as ethynyloxy, propargyloxy, butynyloxy, etc. In particular, propargyloxy is preferred. The haloalkoxy includes, for example, the above alkoxy which is substituted by at least one halogen atom (e.g., fluorine, chlorine, bromine, iodine) such as difluoromethoxy, trifluoromethoxy, chloromethoxy, etc. In particular, difluoromethoxy is preferred. The aryloxy includes, for example, aryloxy having 6 to 12 carbon atoms, preferably 6 to 8 carbon atoms, such as phenoxy, naphthoxy, etc.

Examples of the alkylthio as the substituent of the optionally substituted aryl represented by R¹² or R¹³ include alkylthio having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms, more preferably 1 to 2 carbon atoms, such as methylthio, ethylthio, propylthio, butylthio, etc. In particular, methylthio is preferred.

Examples of the optionally substituted amino as the substituent of the optionally substituted aryl represented by R¹² or R¹³ include amino, amino which is mono- or di-substituted by alkyl having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms (e.g., monomethylamino, dimethylamino, monoethylamino, etc.), etc.

The optionally substituted heterocyclic group represented by R¹² or R¹³ includes, for example, heterocyclic groups containing 1 to 4, preferably 1 to 2 heteroatoms (e.g., oxygen, nitrogen, sulfur, etc.). At any possible position, the heterocycle has the bond to the methylene carbon atom in the formula (a). Examples of the heterocyclic group include pyridyl, pyridazinyl, pyrazolyl, pyrimidinyl, furyl, thienyl, oxazolyl, isoxazolyl, benzothiazolyl, quinolyl, quinazolinyl, pyrazinyl, morpholino, piperazinyl, etc. Preferred examples thereof include furyl (e.g., 2-furyl, etc.), thienyl (e.g., 2-thienyl, etc.), pyridyl (2-pyridyl, etc.), pyrazinyl (e.g., 2-pyrazinyl, etc.), pyrimidinyl (e.g., 2-pyrimidinyl, etc.), and morpholino. The heterocyclic group is unsubstituted or substituted. The substituent includes the above substituents of the optionally substituted aryl represented by R¹² or R¹³.

The monocyclic or polycyclic ring which is formed by R¹² and R¹³ and may contain (a) heteroatom(s) is a 4- to 8-membered ring which is formed by R¹² and R¹³ with the carbon atom to which they are attached. The ring may contain at least one heteroatom (e.g., oxygen, nitrogen, sulfur, etc) and may form a condensed ring with another ring. Examples of the ring include cyclopentane, cyclohexane, indan, 1,2,3,4-tetrahydronaphthalene, 5,6,7,8-tetrahydroquinoline, 4,5,6,7-tetrahydrobenzo b!furan, etc. The ring has a bivalent bond at any possible position.

The optionally substituted (substituted imino)methyl represented by Q is represented, for example, by the formula (b): ##STR26## wherein R¹⁴ and R¹⁵ have the same meanings as the above R¹² and R¹³, respectively.

The alkyl of the optionally substituted alkyl represented by Q includes the alkyl represented by R¹. The alkenyl of the optionally substituted alkenyl represented by Q includes, for example, alkenyl having 2 to 8 carbon atoms, preferably 3 to 6 carbon atoms, such as allyl, propenyl, isopropenyl, butenyl, isobutenyl, pentenyl, hexenyl, hexadienyl, etc. The alkynyl of the optionally subsititued alkynyl represented by Q includes, for example, alkynyl having 2 to 6 carbon atoms, preferably 2 to 4 carbon atoms, such as propargyl, ethynyl, butynyl, etc. When the alkyl, alkenyl and alkynyl are substituted, the substituents are, for example, the above halogen atom, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl and substituted amino, each of which is represented by R¹ ; the above optionally substituted phenyl, optionally substituted naphthyl, and optionally substituted heterocyclic group, each of which is represented by Q; etc.

The substituted carbonyl represented by Q includes, for example, (optionally substituted alkyl)carbonyl, (optionally substituted phenyl)carbonyl, (optionally substituted naphthyl)carbonyl, (optionally substituted heterocyclic group)carbonyl, etc.

The substituted sulfonyl represented by Q includes, for example, (optionally substituted alkyl)sulfonyl, (optionally substituted phenyl)sulfonyl, (optionally substituted naphthyl)sulfonyl, (optionally substituted heterocyclic group)sulfonyl, etc.

The optionally substituted alkyl in the above substituted carbonyl or substituted sulfonyl includes the above optionally substituted alkyl represented by R¹. The optionally substituted phenyl, optionally substituted naphthyl, and optionally substituted heterocyclic group include the corresponding groups represented by Q.

Q is preferably a group of the formula (XX); pyridyl, pyrimidinyl, quinolyl, quinazolinyl, benzothiazolyl or pyrazolyl, each of which is unsubstituted or substituted; or a group of the formula (a).

X is a hydrogen atom, halogen atom, optionally substituted alkyl or optionally substituted hydroxyl. This is intended to include a case where the phenylene group in the above formula (I) is unsubstituted, i.e., X is a hydrogen atom; and a case wherein the phenylene group is substituted at any possible position by 1 to 3 substituents selected from a halogen atom, optionally substituted alkyl and optionally substituted hydroxyl. When the phenylene group is substituted by 2 or 3 substituents, the substituents are the same or different.

The halogen atom, optionally substituted alkyl and optionally substituted hydroxyl represented by X include, for example, the corresponding groups represented by R¹, respectively.

X is preferably a hydrogen atom.

The optionally substituted hydroxyl and alkylthio represented by Y include, for example, the corresponding groups represented by R¹. In particular, methoxy is preferred.

The optionally substituted amino represented by Y is represented, for example, by the formula (XXI):

    --NR.sup.5 R.sup.6                                         (XXI)

wherein R⁵ is a hydrogen atom or alkyl; R⁶ is a hydrogen atom, alkyl or hydroxylalkyl. The alkyl represented by R⁵ or R⁶ and the alkyl of the hydroxylalkyl represented by R⁶ include, for example, the above alkyl represented by R¹. Preferably, R⁵ and R⁶ are the same or different and are a hydrogen atom or alkyl (preferably methyl). More preferably, the group of the formula (XXI) as Y is monoalkylamino, particularly preferably monomethylamino.

Y is preferably alkoxy or a group of the formula (XXI), more preferably methoxy or monoalkylamino (preferably monomethylamino).

Z is preferably an oxygen atom.

The alkyl represented by R² includes, for example, the above alkyl represented by R¹. In particular, methyl is preferred.

The acyl represented by R² includes formyl; alkylcarbonyl containing alkyl having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms (e.g., acetyl, propionyl, butyryl, etc.); benzoyl; etc. In particular, acetyl is preferred.

M is preferably an oxygen atom, sulfur atom or NR², more preferably an oxygen atom.

n is preferably 0 or 1.

The compound of the formula (I) of the present invention has an asymmetric carbon atom at the 2-position. Each optical isomer and mixtures thereof are included in the present invention.

Preferred examples of the compound of the formula (I) are that wherein:

X is a hydrogen atom, R¹ is hydroxyl, Z is an oxygen atom, Y is amino optionally substituted by alkyl, M is an oxygen atom, Q is optionally substituted phenyl, and n is 0 or 1;

X is a hydrogen atom, R¹ is alkoxy, Z is an oxygen atom, Y is alkoxy or optionally substituted amino, M is an oxygen atom, Q is optionally substituted phenyl, and n is 0 or 1;

X is a hydrogen atom, R¹ is hydroxyl, Z is an oxygen atom, Y is amino optionally substituted by alkyl, M is an oxygen atom, Q is an optionally substituted heterocyclic group, and n is 0 or 1;

X is a hydrogen atom, R¹ is alkoxy, Z is an oxygen atom, Y is alkoxy or optionally substituted amino, M is an oxygen atom, Q is an optionally substituted heterocyclic group, and n is 0 or 1;

X is a hydrogen atom, R¹ is alkoxy, Z is an oxygen atom, Y is amino optionally substituted by alkyl, M is an oxygen atom, Q is a group of the formula (a), R¹² is alkyl, R¹³ is optionally substituted phenyl or optionally substituted morpholino, and n is 1; or

X is a hydrogen atom, R¹ is alkoxy, Z is an oxygen atom, Y is amino optionally substituted by alkyl, M is acylamino, Q is a group of the formula (a), R¹² is alkyl, R¹³ is optionally substituted phenyl or optionally substituted morpholino, and n is 1.

More preferred examples of the compound of the formula (I) are that wherein:

X is a hydrogen atom, R¹ is hydroxyl, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is phenyl, and n is 0 (Compound No. 1);

X is a hydrogen atom, R¹ is hydroxyl, Z is an oxygen atom, Y is amino, M is an oxygen atom, Q is phenyl, and n is 0 (Compound No. 2);

X is a hydrogen atom, R¹ is hydroxyl, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is 3,4-dimethylphenyl, and n is 0 (Compound No. 15);

X is a hydrogen atom, R¹ is hydroxyl, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is 3,5-dimethylphenyl, and n is 0 (Compound No. 16);

X is a hydrogen atom, R¹ is hydroxyl, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is 2-methylphenyl, and n is 1 (Compound No. 64);

X is a hydrogen atom, R¹ is hydroxyl, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is 2,5-dimethylphenyl, and n is 1 (Compound No. 75);

X is a hydrogen atom, R¹ is hydroxyl, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is 4-chloro-2-methylphenyl, and n is 1 (Compound No. 113);

X is a hydrogen atom, R¹ is methoxy, Z is an oxygen atom, Y is methoxy, M is an oxygen atom, Q is 2,5-dimethylphenyl, and n is 1 (Compound No. 139);

X is a hydrogen atom, R¹ is methoxy, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is 2,5-dimethylphenyl, and n is 1 (Compound No. 140);

X is a hydrogen atom, R¹ is methoxy, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is 4-chloro-2-methylphenyl, and n is 1 (Compound No. 186);

X is a hydrogen atom, R¹ is methoxy, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is 2-methylphenyl, and n is 1 (Compound No. 197);

X is a hydrogen atom, R¹ is methoxy, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is 3-chloro-5-trifluoromethylpyridin-2-yl, and n is 1 (Compound No. 427);

X is a hydrogen atom, R¹ is methoxy, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is 3,5-dichloropyridin-2-yl, and n is 1 (Compound No. 433);

X is a hydrogen atom, R¹ is methoxy, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is 3-trifluoromethyl-5-chloropyridin-2-yl, and n is 1 (Compound No. 448);

X is a hydrogen atom, R¹ is methoxy, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is 3-chloropyridin-2-yl, and n is 1 (Compound No. 466);

X is a hydrogen atom, R¹ is methoxy, Z is an oxygen atom, Y is monomethylamino, X is an oxygen atom, Q is α-methyl-4-chlorobenzylideneamino, and n is 1 (Compound No. 474);

X is a hydrogen atom, R¹ is methoxy, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is α-methyl-4-methoxybenzylideneamino, and n is 1 (Compound No. 492);

X is a hydrogen atom, R¹ is methoxy, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is 4,α-dimethylbenzylideneamino, and n is 1 (Compound No. 498); or

X is a hydrogen atom, R¹ is methoxy, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is α-methyl-4-trifluoromethylbenzylideneamino, and n is 1 (Compound No. 526).

The compounds of the present invention included in the formula (I) can preferably be prepared as follows.

Method A ##STR27## wherein each symbol is as defined above.

The compound of the formula (I-1) of the present invention can be prepared by reducing the compound (II).

The reducing agent to be used is a conventional reducing agent for reduction of ketones, such as metal hydrides, metal hydride complex compounds, etc. Examples of the reducing agent include three-coordinate borane (e.g., borane, etc.), four-coordinate borate (e.g., sodium borohydride, lithium borohydride, etc.), three-coordinate aluminium (e.g., diisobutylaluminum hydride, etc.), four-coordinate alumininate complex (e.g., lithium aluminum hydride, etc.), etc. The amount of the reducing agent to be used is 0.25 to 3 mol, preferably 1.0 to 1.2 mol, per mol of the compound (II).

Examples of the solvent include alcohols such as methanol, ethanol, etc.; ethers such as diethyl ether, tetrahydofuran, etc.; water, etc. These solvents can be used alone or as a mixture thereof.

The reaction temperature is appropriately selected from the range of -20° C. to a reflux temperature of the solvent, and is preferably 0 to 50° C. The reaction time is 0.5 hour to 24 hours, preferably 0.5 to 2 hours.

The compound (I-1) of the present invention thus obtained can be separated and purified by known methods (e.g., chromatography, recrystallization, etc.).

The compound (II) used as the starting material in this reaction can be prepared, for example, according to JP-A 3-246268, JP-A 5-97768 or JP-A 5-331124, for example, by reacting the corresponding halogenated phenyl with butyllithium or magnesium, and then reacting the resulting compound with dialkyl oxalate. Alternatively, it can be prepared by Method Q described below.

Method B ##STR28## wherein R³ is alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxyalkyl, alkylcarbonyl, (alkylthio)carbonyl, alkylsulfonyl, arylsulfonyl or mono- or di-alkyl-substituted carbamoyl, L is a leaving group or R³ --L represents dihydropyran, and the other symbols are as defined above.

The groups represented by R³ are, for example, groups corresponding to the substituents of the above substituted hydroxyl represented by R¹. The leaving group represented by L includes, for example, halogen atoms (e.g., fluorine, chlorine, bromine, iodine), alkylsulfonyloxy (e.g., methanesulfonyloxy, etc.), etc.

The compound (I-2) of the present invention can be prepared by reacting the compound (I-1) of the present invention with the compound (XXII) to introduce alkyl, alkenyl, alkynyl, carbonyl, sulfonyl, carbamoyl or tetrahydropyranyl into the compound (I-1).

The alkyl, alkenyl and alkynyl can be introduced, for example, by using as the compound (XXII) an alkyl halide, alkenyl halide and alkynyl halide, respectively, in the presence of a base. The alkyl halide includes, for example, methyl chloride, methyl bromide, methyl iodide, ethyl chloride, ethyl bromide, ethyl iodide, 1-iodopropane, 2-iodopropane, 1-iodobutane, chlorotrifluoromethane, 1,2-dibromoethane, chloromethyl ether, etc. The alkenyl halide includes, for example, allyl bromide, etc. The alkynyl halide includes, for example, propargyl bromide, etc. The amount of the halide to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (I-1).

Examples of the base include organic bases (e.g., sodium methoxide, sodium ethoxide, potassium t-butoxide, etc.), inorganic bases (e.g., sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride, etc.), etc. The amount of the base to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (I-1).

Examples of the solvent include ethers such as diethyl ether, tetrahydrofuran, etc.; N,N-dimethylformamide, dimethyl sulfoxide, toluene, etc.

The reaction temperature is appropriately selected from the range of -20° C. to a reflux temperature of the solvent, and is preferably 0 to 50° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 10 hours.

The carbonyl can be introduced, for example, by using as the compound (XXII) an acid halide (e.g., acetyl chloride, acetyl bromide, propionyl chloride, thioacetyl chloride, etc.) or acid anhydride (e.g., acetic anhydride, propionic anhydride, etc.) in the presence of a base. The amount of the acid halide or acid anhydride to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (I-1).

Examples of the base include organic bases (e.g., triethylamine, N,N-dimethylaniline, pyridine, etc.) or inorganic bases (sodium carbonate, potassium carbonate, sodium hydride, etc.). The amount of the base to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (I-1).

Examples of the solvent include halogenated hydrocarbons such as methylene chloride, chloroform, etc.; ethers such as diethyl ether, tetrahydrofuran, etc.; N,N-dimethylformamide, dimethyl sulfoxide, toluene, etc.

The reaction temperature is appropriately selected from the range of -20° C. to a reflux temperature of the solvent, and is preferably 0 to 50° C. The reaction time is 0.5 hour to 24 hours, preferably 0.5 to 5 hours.

The sulfonyl can be introduced, for example, by using as the compound (XXII) an alkylsulfonyl halide (e.g., alkylsulfonyl chloride such as methanesulfonyl chloride, ethanesulfonyl chloride, etc.) or arylsulfonyl halide (e.g., arylsulfonyl chloride such as benzenesulfonyl chloride, p-toluenesulfonyl chloride, etc.) in the presence of a base. The amount of the alkylsulfonyl halide or arylsulfonyl halide to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (I-1).

Examples of the base include organic bases (e.g., triethylamine, N,N-dimethylaniline, pyridine, etc.) or inorganic bases (e.g., sodium carbonate, potassium carbonate, sodium hydride, etc.). The amount of the base to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (I-1).

Examples of the solvent include halogenated hydrocarbons such as methylene chloride, chloroform, etc.; ethers such as diethyl ether, tetrahydrofuran, etc.; N,N-dimethylformamide, dimethyl sulfoxide, toluene, etc.

The reaction temperature is appropriately selected from the range of -20° C. to a reflux temperature of the solvent, and is preferably 0 to 50° C. The reaction time is 0.5 hour to 24 hours, preferably 0.5 to 5 hours.

The carbamoyl can be introduced, for example, by using as the compound (XXII) an N-unsubstituted or N-alkyl substituted carbamoyl halide (e.g., monoethylcarbamoyl chloride, dimethylcarbamoyl chloride, etc.). The amount of the carbamoyl halide to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (I-1).

Examples of the base include organic bases (e.g., triethylamine, N,N-dimethylaniline, pyridine, etc.) or inorganic bases (e.g., sodium carbonate, potassium carbonate, sodium hydride, etc.). The amount of the base to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (I-1).

Examples of the solvent include halogenated hydrocarbons such as methylene chloride, chloroform, etc.; ethers such as diethyl ether, tetrahydrofuran, etc.; N,N-dimethylformamide, dimethyl sulfoxide, toluene, etc.

The reaction temperature is appropriately selected from the range of -20° C. to a reflux temperature of the solvent, and is preferably 20 to 70° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 12 hours.

The tetrahydropyranyl can be introduced by a conventional method for protecting a hydroxyl group with tetrahydropyranyl, for example, according to the same manner as in Method Y described below.

The compound (I-2) of the present invention thus obtained can be separated and purified by conventional methods (e.g., chromatography, recrystallization, etc.).

Method C ##STR29## wherein each symbol is as defined above.

The compound (I-4) of the present invention can be prepared by reacting the compound (I-3) of the present invention with a sulfuring agent (i.e., sulfur-introducing agent).

The sulfuring agent includes, for example, phosphorus pentasulfide and Lawesson's reagent. The amount of the sulfuring agent to be used is 1 to 5.mol, preferably 1 to 2 mol, per mol of the compound (I-3).

Examples of the solvent include aromatic hydrocarbons such as toluene, xylene, etc; and pyridine. These solvents can be used alone or as a mixture thereof.

The reaction temperature is appropriately selected from the range of room temperature to a reflux temperature of the solvent, and is preferably 80° C. to 150° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 12 hours.

The compound (I-4) of the present invention thus obtained can be separated and purified by known methods (e.g., chromatography, recrystallization, etc.).

Method D ##STR30## wherein R⁴ is alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl or alkoxyalkyl, R⁵ is a hydrogen atom or alkyl, R⁶ is a hydrogen atom, alkyl or hydroxyalkyl, Y¹ is alkoxy or alkylthio, and the other symbols are as defined above.

The groups represented by R⁴ are, for example, groups corresponding to the substituents of the above substituted hydroxyl represented by R¹. The alkoxy and alkylthio represented by Y¹ include, for example, the above alkoxy and alkylthio represented by R¹, respectively.

The compound (IV-2) of the present invention can be prepared by reacting the compound (IV-1) with an amine.

The amine includes compounds of the formula (V): R⁵ R⁶ NH (wherein R⁵ and R⁶ are as defined above). Examples thereof include liquid ammonia; primary amines such as methylamine, ethylamine, etc.; secondary amines such as dimethylamine, diethylamine, etc. The amount of the amine to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (IV-1).

Examples of the solvent include alcohols such as methanol, ethanol, etc.; aromatic hydrocarbons such as toluene, xylene, etc.; halogenated hydrocarbons such as methylene chloride, chloroform, etc.; ethers such as ether, tetrahydrofuran, etc.; and water. These solvents can be used alone or as a mixture thereof.

The reaction temperature is appropriately selected from the range of 0° C. to a reflux temperature of the solvent, and is preferably 20° C. to 80° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 12 hours.

The compound (IV-2) of the present invention thus obtained can be separated and purified by known methods (e.g., chromatography, recrystallization, etc.).

Method E ##STR31## wherein A is a halogen atom, and the other symbols are as defined above.

The halogen atom represented by A includes, for example, fluorine, chlorine, bromine and iodine.

The compound (I-5) of the present invention can be prepared by halogenating the compound (I-1) of the present invention. The halogenating agent to be used in the halogenation includes, for example, chlorinating agents such as thionyl chloride, phosphorus oxychloride, phosphorus pentachloride, carbon tetrachloride - triphenylphosphine, etc.; brominating agents such as thionyl bromide, phosphorus tribromide, carbon tetrabromide - triphenylphosphine, etc. The amount of the halogenating agent to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (I-1).

Examples of the solvent include aromatic hydrocarbons such as toluene, xylene, etc.; halogenated hydrocarbons such as methylene chloride, chloroform, etc.; ethers such as ether, tetrahydrofuran, etc.

The reaction temperature is appropriately selected from the range of 0° C. to a reflux temperature of the solvent, and is preferably 20° C. to 80° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 12 hours.

The compound (I-5) of the present invention thus obtained can be separated and purified by known methods (e.g., chromatography, recrystallization, etc.).

Method F ##STR32## wherein R⁷ is alkyl, m is 1 or 2, and the other symbols are as defined above.

The alkyl represented by R⁷ includes, for example, the above alkyl represented by R¹.

The compound (XII) of the present invention can be prepared by oxidizing the compound (XI) of the present invention. The oxidizing agent to be used in the oxidation includes, for example, hydrogen peroxide, peracids such as peracetic acid, perbenzoic acid, m-chloroperbenzoic acid, etc., sodium metaperiodate, hydroperoxide, etc. The amount of the oxidizing agent to be used is 1 to 10 mol, preferably 1 to 3 mol, per mol of the compound (XI).

Examples of the solvent include aromatic hydrocarbons such as toluene, xylene, etc.; halogenated hydrocarbons such as methylene chloride, chloroform, etc.; ethers such as ether, tetrahydrofuran, etc., alcohols such as methanol, ethanol, etc.; and water. These solvents can be used alone or as a mixture thereof.

The reaction temperature is appropriately selected from the range of -20° C. to a reflux temperature of the solvent, and is preferably 0° C. to 50° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 12 hours.

The compound (XII) of the present invention thus obtained can be separated and purified by known methods (e.g., chromatography, recrystallization, etc.).

Method G ##STR33## wherein A is a halogen atom, B is optionally substituted hydroxyl, alkylthio, amino optionally substituted by alkyl, or nitro, and the other symbols are as defined above.

The groups represented by B include, for example, the above corresponding groups represented by R¹.

The compound (I-6) of the present invention can be prepared by reacting the compound (I-5) of the present invention with a nucleophile to displace the group A.

For example, when A is displaced by substituted hydroxyl, for example, a metal salt of an alcohol (e.g., sodium methoxide, sodium 2-propenoxide, potassium 2-propynoxide, potassium 2,2,2-trifluoroethoxide, sodium methoxymethoxide, etc.) may directly be used as the nucleophile, or a metal salt of an alcohol is formed in the reaction mixture from an alcohol and a metal hydride (e.g., sodium hydride, potassium hydride, etc.) to use it in the reaction. In both cases, the amount of the metal salt of an alcohol to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (I-5).

Examples of the solvent to be used include aromatic hydrocarbons such as toluene, xylene, etc.; halogenated hydrocarbons such as methylene chloride, chloroform, etc.; ethers such as ether, tetrahydrofuran, etc.; N,N-dimethylformamide, and dimethyl sulfoxide.

The reaction temperature is appropriately selected from the range of 0° C. to a reflux temperature of the solvent, and is preferably 20° C. to 80° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 12 hours.

When the group A is displaced by alkylthio, for example, a metal salt of an alkylmercaptan (e.g., sodium thiomethoxide, sodium thioethoxide, etc.) may directly be used as the nucleophile, or a metal salt of an alkylmercaptan is formed in the reaction mixture from an alkylmercaptan and a metal hydride (e.g., sodium hydride, potassium hydride, etc.) or a hydroxide (e.g., sodium hydroxide, potassium hydroxide, etc.) to use it in the reaction. In both cases, the amount of the metal salt of an alkylmercaptan to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (I-5).

Examples of the solvent to be used include aromatic hydrocarbons such as toluene, xylene, etc.; ethers such as ether, tetrahydrofuran, etc.; acetonitrile, N,N-dimethylformamide, dimethyl sulfoxide, and water. These solvents can be used alone or as a mixture thereof.

The reaction temperature is appropriately selected from the range of 0° C. to a reflux temperature of the solvent, and is preferably 20° C. to 80° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 12 hours.

When the group A is displaced by amino optionally substituted by alkyl, for example, an amine (e.g., liquid ammonia, ammonia water, monomethylamine, dimethylamine, etc.) is used as the nucleophile in an amount of 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (I-5).

Examples of the solvent to be used include aromatic hydrocarbons such as toluene, xylene, etc.; ethers such as ether, tetrahydrofuran, etc.; alcohols such as methanol, ethanol, etc.; N,N-dimethylformamide, dimethyl sulfoxide, and water. These solvents can be used alone or as a mixture thereof.

The reaction temperature is appropriately selected from the range of -20° C. to a reflux temperature of the solvent, and is preferably 0° C. to 80° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 12 hours.

When the group A is displaced by nitro, for example, a nitrite (e.g., sodium nitrite, potassium nitrite, etc.) is used as the nucleophile in an amount of 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (I-5). In addition, phloroglucinol is used in an amount of 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (I-5).

Examples of the solvent to be used include aromatic hydrocarbons such as toluene, xylene, etc.; ethers such as ether, tetrahydrofuran, etc.; alcohols such as methanol, ethanol, etc.; N,N-dimethylformamide, and dimethyl sulfoxide.

The reaction temperature is appropriately selected from the range of 0° C, to a reflux temperature of the solvent, and is preferably 20° C. to 80° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 12 hours.

The compound (I-6) of the present invention thus obtained can be separated and purified by known methods (e.g., chromatography, recrystallization, etc.).

Method H ##STR34## wherein R⁸ is alkyl, haloalkyl or alkoxyalkyl, Y³ is hydroxyl or amino, and the other symbols are as defined above.

The groups represented by R⁸ include, for example, the above corresponding groups represented by R¹.

The compound (XV) of the present invention can be prepared by hydrolyzing the compound (XIV) with an acid or base.

Examples of the acid include mineral acids (e.g., hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.) and organic acids (e.g., formic acid, acetic acid, etc.). These acids can be used alone or as a mixture thereof. Examples of the base include organic bases (e.g., sodium ethoxide, etc.) and inorganic bases (e.g., sodium hydroxide, potassium hydroxide, etc.). The amount of the acid or base to be used is 1 to 10 mol, preferably 1 to 3 mol, per mol of the compound (XIV).

Examples of the solvent to be used include aromatic hydrocarbons such as toluene, xylene, etc.; ethers such as ether, tetrahydrofuran, etc.; alcohols such as methanol, ethanol, etc.; N,N-dimethylformamide, dimethyl sulfoxide, water, etc. These solvents can be used alone or as a mixture thereof.

The reaction temperature is appropriately selected from the range of -80° C. to a reflux temperature of the solvent, and is preferably 0° C. to 80° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 6 hours.

The compound (XV) of the present invention thus obtained can be separated and purified by known methods (e.g., chromatography, recrystallization, etc.).

The compound (XIV) used as the starting material in this reaction can be prepared, for example, by Method R described below.

Method I ##STR35##

wherein Y⁴ is alkoxy, mono- or di-alkyl-substituted amino, and the other symbols are as defined above.

The groups represented by Y⁴ include the above corresponding groups represented by R¹.

The compound (XVI) of the present invention can be prepared by alkylating the compound (XV) of the present invention. The alkylation can be carried out using an alkyl halide in the presence of a base. Examples of the alkyl halide include methyl chloride, methyl bromide, methyl iodide, ethyl chloride, ethyl bromide, ethyl iodide, 1-iodopropane, 2-iodopropane, 1-iodobutane, etc. The amount of the alkyl halide to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (XV).

Examples of the base include organic bases (e.g., butyllithium, sodium ethoxide, etc.) and inorganic bases (e.g., sodium hydroxide, potassium hydroxide, sodium amide, sodium hydride, etc.). The amount of the base to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (XV).

Examples of the solvent to be used include aromatic hydrocarbons such as toluene, xylene, etc.; halogenated hydrocarbons such as methylene chloride, chloroform, etc.; ethers such as ether, tetrahydrofuran, etc.; alcohols such as methanol, ethanol, etc.; N,N-dimethylformamide, dimethyl sulfoxide, etc.

The reaction temperature is appropriately selected from the range of -80° C. to a reflux temperature of the solvent, and is preferably 0° C. to 80° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 6 hours.

The compound (XVI) of the present invention thus obtained can be separated and purified by known methods (e.g., chromatography, recrystallization, etc.).

Method J ##STR36## wherein each symbol is as defined above.

The compound (X) of the present invention can be prepared by hydrolyzing the compound (I) of the present invention in an appropriate solvent.

The hydrolysis can be carried out by treating the compound (I) with a base. Examples of the base include organic bases (e.g., metal alkoxides such as sodium ethoxide, etc.) and inorganic bases (e.g., metal hydroxides such as sodium hydroxide, potassium hydroxide, etc.). The amount of the base to be used is 1 to 10 mol, preferably 1 to 3 mol, per mol of the compound (I).

Examples of the solvent to be used include aromatic hydrocarbons such as toluene, xylene, etc.; ethers such as ether, tetrahydrofuran, etc.; alcohols such as methanol, ethanol, etc.; N,N-dimethylformamide, dimethyl sulfoxide, water, etc. These solvents can be used alone or in combination thereof.

The reaction temperature is appropriately selected from the range of -80° C. to a reflux temperature of the solvent, and is preferably 0° C. to 80° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 6 hours.

The compound (X) of the present invention thus obtained can be separated and purified by known methods (e.g., chromatography, recrystallization, etc.).

Method K ##STR37## wherein R¹¹ is alkyl, alkenyl or alkynyl, and the other symbols are as defined above.

The compound (XVII) of the present invention can be prepared by reacting the compound (X) of the present invention with the compound (XIII).

This reaction can be carried, for example, by using an alkyl halide, alkenyl halide or alkynyl halide as the compound (XIII) in the presence of a base. The alkyl halide includes, for example, methyl chloride, methyl bromide, methyl iodide, ethyl chloride, ethyl bromide, ethyl iodide, 1-iodopropane, 2-iodopropane, 1-iodobutane, chlorotrifluoromethane, 1,2-dibromoethane, chloromethyl ether, etc. The alkenyl halide includes, for example, allyl bromide, etc. The alkynyl halide includes, for example, propargyl bromide, etc. The amount of the halide to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (X).

Examples of the base include organic bases (e.g., sodium methoxide, sodium ethoxide, potassium t-butoxide, etc.), inorganic bases (e.g., sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride, etc.), etc. The amount of the base to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (X).

Examples of the solvent to be used include ethers such as diethyl ether, tetrahydrofuran, etc.; N,N-dimethylformamide, dimethyl sulfoxide, toluene, etc.

The reaction temperature is appropriately selected from the range of -20° C. to a reflux temperature of the solvent, and is preferably 0° C. to 50° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 10 hours.

The compound (XVII) of the present invention thus obtained can be separated and purified by known methods (e.g., chromatography, recrystallization, etc.).

Method L ##STR38## wherein J is a hydrogen atom or a metal salt, and the other symbols are as defined above.

The compound (I) of the present invention can be prepared by halogenating the compound (X) of the present invention, and then reacting the resulting compound with the compound (XXVIII).

Examples of the metal salt represented by J include alkaline metal salts (sodium salt, potassium salt, etc.), alkaline earth metal salts (magnesium salt, calcium salt, etc.), etc.

The halogenation is carried out, for example, by using a sulfonyl halide in an amount of 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (X) in the presence of a catalytic amount of a base such as N,N-dimethylformamide.

The sulfonyl halide includes, for example, sulfonyl chloride and sulfonyl bromide.

Examples of the solvent to be used include halogenated hydrocarbons such as methylene chloride, 1,2-dichloroethane, etc.; ethers such as diethyl ether, etc.; aromatic hydrocarbons such as toluene, etc.

The reaction temperature is appropriately selected from the range of room temperature to a reflux temperature of the solvent. The reaction time is 0.5 hour to 24 hours, preferably 1 to 5 hours.

The acid halide thus obtained can be used in the next step without purification.

The acid halide can be reacted with an alcohol, mercaptan, amine or its metal salt YJ (XXVIII) in the presence of a base to convert it to the compound (I).

Examples of the base include organic bases (e.g., triethylamine, N,N-dimethylaniline, pyridine, etc.) and inorganic bases (e.g., sodium carbonate, potassium carbonate, sodium hydride, etc.). The amount of the base to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the acid halide.

Examples of the solvent to be used include halogenated hydrocarbons such as methylene chloride, 1,2-dichloroethane, etc.; ethers such as diethyl ether, etc.; aromatic hydrocarbons such as toluene, etc.; dimethyl sulfoxide, N,N-dimethylformamide, etc.

The reaction temperature is appropriately selected from the range of 0° C. to a reflux temperature of the solvent, and is preferably 0° C. to room temperature. The reaction time is 0.5 hour to 24 hours, preferably 0.5 to 2 hours.

The compound (I) of the present invention thus obtained can be separated and purified by known methods (e.g., chromatography, recrystallization, etc.).

Method M ##STR39## wherein D is a halogen atom, and the other symbols are as defined above.

The compound (I) of the present invention can be prepared by reacting the compound (XVIII) with the compound (XIX) in an appropriate solvent.

The halogen atom represented by D in the above formula includes, for example, fluorine, chlorine, bromine, and iodine.

The amount of the compound (XIX) to be used is 1 to 3 mol, preferably 1 to 1.5 mol, per mol of the compound (XVIII).

This reaction is preferably carried out in the presence of a base. Examples of the base include organic bases (e.g., alkoxides such as sodium methoxide, sodium ethoxide, potassium t-butoxide, etc.; amines such as pyridine, triethylamine, etc.), inorganic bases (e.g., metal hydroxides such as sodium hydroxide, potassium hydroxide, etc.; metal carbonates such as sodium carbonate, potassium carbonate, etc.; hydrides such as sodium hydride, potassium hydride, etc.), etc. The amount of the base to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (XVIII).

Examples of the solvent to be used include ethers such as diethyl ether, tetrahydrofuran, etc.; N,N-dimethylformamide, dimethyl sulfoxide, toluene, etc.

The reaction temperature is appropriately selected from the range of -20° C. to a reflux temperature of the solvent, and is preferably 0 to 50° C. The reaction time is 0.5 hour to 72 hours, preferably 0.5 to 10 hours.

The compound (I) of the present invention thus obtained can be separated and purified by known methods (e.g., chromatography, recrystallization, etc.).

Method N ##STR40## wherein L is a leaving group, and the other symbols are as defined above.

The compound (I) of the present invention can be prepared by reacting the compound (XXIII) with the compound (XXIV).

In the compound (XXIV), L is attached to any possible position in Q. Preferred examples of the compound (XXIV) include alkyl halides (e.g., methyl chloride, methyl bromide, methyl iodide, ethyl chloride, ethyl bromide, ethyl iodide, 1-iodopropane, 2-iodopropane, 1-iodobutane, chlorotrifluoromethane, 1,2-dibromoethane, chloromethyl ether, etc.); alkenyl halides (e.g., allyl bromide; etc.); alkynyl halides (e.g., propargyl bromide, etc.); acid halides (e.g., acetyl chloride, acetyl bromide, propionyl chloride, thioacetyl chloride, etc.); acid anhydrides (e.g., acetic anhydride, propionic anhydride, etc.); alkylsulfonyl halides (e.g., alkylsulfonyl chlorides such as methanesulfonyl chloride, ethanesulfonyl chloride, etc.); arylsulfonyl halides (e.g., arylsulfonyl chlorides such as benzenesulfonyl chloride, p-toluenesulfonyl chloride, etc.); N-unsubstituted or N-alkyl substituted carbamoyl halides (e.g., monoethylcarbamoyl chloride, dimethylcarbamoyl chloride, etc.); pyridine and its derivatives (e.g., 2,3-dichloropyridine, 2,5-dichloropyridine, 2-chloro-3-trifluoromethylpyridine, 2-chloro-5-trifluoromethylpyridine, 2-chloro-3-methylpyridne, 2,3,5-trichloropyridine, 2,3-dichloro-5-trifluoromethylpyridine, 2,5-dichloro-3-trifluoromethylpyridine, etc.); pyrimidine and its derivatives (e.g., 4,6-dichloropyrimidine, 2-chloro-4,6-dimethylpyrimidine, 4-chloro-5-ethoxycarbonyl-6-ethylpyrimidine, etc.); pyrazole and its derivatives (e.g., 5-chloro-4-formyl-1-methylpyrazole, 5-chloro-4-methoxycarbonyl-1,3-dimethylpyrazole, etc.); quinoline and its derivatives (e.g., 4-chloroquinoline, etc.); benzothiazole and its derivatives (e.g., 2-chlorobenzothiazole, etc.); quinazoline and its derivatives (e.g., 4-chloroquinazoline, etc.); benzene and its derivatives (e.g., 1-iodo-4-nitrobenzene, 1-bromo-4-trifluoromethylbenzene, etc.), etc.

For example, when Q is an optionally substituted aryl group, this reaction is carried out using the compound (XXIV) in an amount of 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (XXIII) in the presence of a base. Examples of the base include organic bases (e.g., triethylamine, N,N-dimethylaniline, pyridine, etc.), inorganic bases (e.g., sodium carbonate, potassium carbonate, sodium hydride, etc.), etc. The amount of the base to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (XXIII). Examples of the solvent include ethers such as tetrahydrofuran, etc.; aromatic hydrocarbons such as toluene, etc.; dimethyl sulfoxide; N,N-dimethylformamide; etc. The temperature is room temperature to 200° C., preferably 100 to 150° C., and the reaction time is 1 to 48 hours, preferably 2 to 24 hours.

For example, when Q is an optionally substituted heterocyclic group, this reaction is carried out using the compound (XXIV) in an amount of 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (XXIII) in the presence of a base. Examples of the base include organic bases (e.g., triethylamine, N,N-dimethylaniline, pyridine, etc.), inorganic bases (e.g., sodium carbonate, potassium carbonate, sodium hydride, etc.), etc. The amount of the base to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (XXIII). Examples of the solvent include ethers such as tetrahydrofuran, etc.; aromatic hydrocarbons such as toluene, etc.; dimethyl sulfoxide; N,N-dimethylformamide; etc. The reaction temperature is 0 to 150° C., preferably room temperature to 80° C. The reaction time is 0.5 to 48 hours, preferably 2 to 12 hours.

For example, when Q is alkyl, alkenyl or alkynyl each of which may be substituted, this reaction is carried out using the compound (XXIV) in an amount of 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (XXIII) in the presence of a base. Examples of the base include organic bases (e.g., sodium methoxide, sodium ethoxide, potassium t-butoxide, etc.), inorganic bases (e.g., sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride, etc.), etc. The amount of the base to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (I-1). Examples of the solvent include ethers such as diethyl ether, tetrahydrofuran, etc.; N,N-dimethylformamide, dimethyl sulfoxide, toluene, etc. The reaction temperature is appropriately selected from the range of -20° C. to a reflux temperature of the solvent, and is preferably 0 to 50° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 10 hours.

For example, when Q is a substituted carbonyl group, this reaction is carried out using the compound (XXIV) in an amount of 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (XXIII) in the presence of a base. Examples of the base include organic bases (e.g., triethylamine, N,N-dimethylaniline, pyridine, etc.) and inorganic bases (e.g., sodium hydroxide, potassium hydroxide, sodium hydride, etc.). The amount of the base to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (XXIII). Examples of the solvent to be used include halogenated hydrocarbons such as methylene chloride, chloroform, etc.; ethers such as diethyl ether, tetrahydrofuran, etc.; N,N-dimethylformamide, dimethyl sulfoxide, toluene, etc. The reaction temperature is appropriately selected from the range of -20° C. to a reflux temperature of the solvent, and is preferably 0 to 70° C., more preferably 20 to 50° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 12 hours, more preferably 0.5 to 5 hours.

For example, when Q is a substituted sulfonyl group, this reaction is carried out using the compound (XXIV) in an amount of 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (XXIII) in the presence of a base. Examples of the base include organic bases (e.g., triethylamine, N,N-dimethylaniline, pyridine, etc.) and inorganic bases (e.g., sodium carbonate, potassium carbonate, sodium hydride, etc.). The amount of the base to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (XXIII). Examples of the solvent to be used include halogenated hydrocarbons such as methylene chloride, chloroform, etc.; ethers such as diethyl ether, tetrahydrofuran, etc.; N,N-dimethylformamide, dimethyl sulfoxide, toluene, etc. The reaction temperature is appropriately selected from the range of -20° C. to a reflux temperature of the solvent, and is preferably 0 to 50° C. The reaction time is 0.5 hour to 24 hours, preferably 0.5 to 5 hours.

The compound (I) of the present invention thus obtained can be separated and purified by known methods (e.g., chromatography, recrystallization, etc.).

Method O ##STR41## wherein R⁹ is tetrahydropyranyl.

The compound (I-1) of the present invention can be prepared by treating the compound (XXV) with an acid.

The tetrahydropyranyl represented by R⁹ includes, for example, 2-tetrahydropyranyl, etc.

The compound (I-1) of the present invention can be prepared by treating the compound (XXV) with an acid in an appropriate solvent.

Examples of the acid to be used in this reaction include mineral acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, etc.; sulfonic acids such as p-toluenesulfonic acid, etc.; acid-base pairs such as pyridinium p-toluenesulfonate, etc.; etc. The amount of the acid to be used is 0.01 to 0.5 mol, preferably 0.05 to 0.2 mol, per mol of the compound (XXV).

Examples of the solvent to be used include alcohols such as methanol, ethanol, etc.; aromatic hydrocarbons such as toluene, xylene, etc.; halogenated hydrocarbons such as methylene chloride, chloroform, etc.; ethers such as ether, tetrahydrofuran, etc.; and water. These solvents can be used alone or as a mixture thereof.

The reaction temperature is appropriately selected from the range of 0° C. to a reflux temperature of the solvent, and is preferably 20° C. to 80° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 12 hours.

The compound (I-1) of the present invention thus obtained can be separated and purified by known methods (e.g., chromatography, recrystallization, etc.).

Method P ##STR42## wherein each symbol is as defined above.

The compound (XXVII) of the present invention can be prepared by oxidizing the compound (XXVI) of the present invention. Examples of the oxidizing agent to be used in the oxidation include peracids such as hydrogen peroxide, peracetic acid, perbenzoic acid, m-chloroperbenzoic acid, etc., sodium metaperiodate, hydroperoxide, etc. The amount of the oxidizing agent to be used is 1 to 10 mol, preferably 1 to 3 mol, per mol of the compound (XXVI).

Examples of the solvent to be used include aromatic hydrocarbons such as toluene, xylene, etc.; halogenated hydrocarbons such as methylene chloride, chloroform, etc.; ethers such as ether, tetrahydrofuran, etc.; alcohols such as methanol, ethanol, etc.; and water. These solvents can be used alone or as a mixture thereof.

The reaction temperature is appropriately selected from the range of -20° C. to a reflux temperature of the solvent, and is preferably 0° C. to 50° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 12 hours.

The compound (XXVII) of the present invention thus obtained can be separated and purified by known methods (e.g., chromatography, recrystallization, etc.).

The following are processes for producing compounds used as the starting material in the above production of the compounds of the present invention.

The compound (II) which can be used as the starting material in the reaction of Method A can preferably be prepared by Method Q described below.

Method Q ##STR43## wherein each symbol is as defined above.

The compound (II) can be prepared by reacting the compound (XXX) with the compound (XIX) in an appropriate solvent in the presence of a base.

The amount of the compound (XIX) to be used is 1 to 3 mol, preferably 1 to 1.5 mol, per mol of the compound (XXX).

Examples of the base include organic bases (e.g., alkoxides such as sodium methoxide, sodium ethoxide, potassium t-butoxide, etc.; amines such as pyridine, triethylamine, etc.), inorganic bases (e.g., metal hydroxides such as sodium hydroxide, potassium hydroxide, etc.; metal carbonates such as sodium carbonate, potassium carbonate, etc.; hydrides such as sodium hydride, potassium hydride, etc.), etc. The amount of the base to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (XXX).

Examples of the solvent to be used include ethers such as diethyl ether, tetrahydrofuran, etc.; N,N-dimethylformamide, dimethyl sulfoxide, toluene, etc.

The reaction temperature is appropriately selected from the range of -20° C. to a reflux temperature of the solvent, and is preferably 0 to 50° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 10 hours.

The compound (II) thus obtained can be used in the next step as the reaction mixture or the crude product, or after separating and purifying it by known methods (e.g., chromatography, recrystallization, etc.).

The compound (XXX) used as the starting material in this reaction can be obtained by halogenating the corresponding alkylphenyl compound according to JP-A 2-3651 or JP-A 2-164866.

The compound (XIV) which can be used as the starting material in the reaction of Method H can preferably be prepared by Method R described below.

Method R ##STR44## wherein R⁸ is alkyl, haloalkyl or alkoxyalkyl, and the other symbols are as defined above.

The compound (XIV) can be obtained by reacting the compound (IX) with the compound (VI).

The groups represented by R⁸ include, for example, the above corresponding groups represented by R¹.

Examples of the compound (VI) include methyl chloride, methyl bromide, methyl iodide, ethyl chloride, ethyl bromide, ethyl iodide, 1-iodopropane, 2-iodopropane, 1-iodobutane, chlorotrifluoromethane, 1,2-dibromoethane, chloromethyl ether, etc. The amount of the compound (VI) to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (IX).

Normally, this reaction is carried out in the presence of a base. Examples of the base include organic bases (e.g., butyllithium, sodium ethoxide, etc.) and inorganic bases (e.g., sodium hydroxide, potassium hydroxide, sodium amide, sodium hydride, etc.). The amount of the base to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the Compound (IX).

Examples of the solvent to be used include aromatic hydrocarbons such as toluene, xylene, etc.; halogenated hydrocarbons such as methylene chloride, chloroform, etc.; ethers such as ether, tetrahydrofuran, etc.; alcohols such as methanol, ethanol, etc.; N,N-dimethylformamide, dimethyl sulfoxide, etc.

The reaction temperature is appropriately selected from the range of -80° C. to a reflux temperature of the solvent, and is preferably 0° C. to 80° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 6 hours.

The compound (XIV) thus obtained can be separated and purified by known methods (e.g., chromatography, recrystallization, etc.).

The compound (XXXIX) included in the compound (XVIII) which can be used as the starting material in the reaction of Method M can preferably be prepared by Method S described below.

Method S ##STR45## wherein R⁵ is a hydrogen atom or alkyl, R⁶ is a hydrogen atom, alkyl or hydroxylalkyl, R¹⁰ is optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl, and the other symbols are as defined above.

The compound (XXXIX) can be prepared by halogenating the compound (XXXVII) in an appropriate solvent.

The alkyl, alkenyl and alkynyl represented by R¹⁰ include the above alkyl, alkenyl and alkynyl as the substituents of the optionally substituted hydroxyl represented by R¹, respectively.

The halogenating agent to be used in this reaction includes, for example, chlorinating agents such as thionyl chloride, phosphorus oxychloride, phosphorus pentachloride, carbon tetrachloride - triphenylphosphine, etc.; and brominating agents such as thionyl bromide, phosphorus oxybromide, carbon tetrabromide - triphenylphosphine, etc. The amount of the halogenating agent to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (XXXVII).

Examples of the solvent to be used include aromatic hydrocarbons such as toluene, xylene, etc.; halogenated hydrocarbons such as methylene chloride, chloroform, etc.; ethers such as ether, tetrahydrofuran, etc.

The reaction temperature is appropriately selected from the range of 0° C. to a reflux temperature of the solvent, and is preferably 20° C. to 80° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 12 hours.

The compound (XXXIX) thus obtained can be used in the next step as the reaction mixture or the crude product, or after separating and purifying it by known methods (e.g., chromatography, recrystallization, etc.).

The compound (XXXVII) which can be used as the starting material in this reaction can preferably be prepared by Method T described below.

Method T ##STR46## wherein each symbol is as defined above.

The compound (XXXVII) can be prepared by reacting the compound (XXXVI) with the compound (V) in an appropriate solvent.

Preferred examples of the compound (V) include liquid ammonia; primary amines such as methylamine, ethylamine, etc.; and secondary amines such as dimethylamine, diethylamine, etc. The amount of the compound (V) to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (XXXVI).

Examples of the solvent to be used include alcohols such as methanol, ethanol, etc.; aromatic hydrocarbons such as toluene, xylene, etc.; halogenated hydrocarbons such as methylene chloride, chloroform, etc.; ethers such as ether, tetrahydrofuran, etc.; and water. These solvents can be used alone or as a mixture thereof.

The reaction temperature is appropriately selected from the range of 0° C. to a reflux temperature of the solvent, and is preferably 20° C. to 80° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 12 hours.

The compound (XXXVII) thus obtained can be used in the next step as the reaction mixture or the crude product, or after separating and purifying it by known methods (e.g., chromatography, recrystallization, etc.).

The compound (XXXVI) which can be used as the starting material in this reaction can preferably be prepared by Method U described below.

Method U ##STR47## wherein Y² is alkoxy, E is a protected hydroxyl group, and the other symbols are as defined above.

The compound (XXXVI) can be prepared by treating the compound (XXXV) with an acid in an appropriate solvent.

The alkoxy represented by Y² in the above formula includes the above alkoxy represented by Y.

The protective group of the protected hydroxyl represented by E include conventional protective groups for hydroxyl such as ether-type protective groups, acetal-type protective groups, etc., described in, for example, T. W. Green, "Protective Groups in Organic Synthesis" p. 1-113, John Willy & Sons (1981); C. B. Reese, "Protective Groups in Organic Chemistry", J. F. McOmie (ed.), p. 95-143, Plenum Press (1973), etc.

Examples of the ether-type protective groups include alkyl (e.g., C₁₋₆ alkyl, preferably C₁₋₄ alkyl, such as methyl, ethyl, propyl, t-butyl, etc.), alkenyl (e.g., C₂₋₆ alkenyl, preferably C₂₋₄ alkenyl, such as allyl, etc.), aralkyl (e.g., substituted or unsubstituted C₆₋₁₀ aryl - C₁₋₄ alkyl such as benzyl, p-methoxybenzyl, triphenylmethyl, etc.), trialkylsilyl (e.g., tri-C₁₋₆ alkylsilyl such as triisopropylsilyl, t-butyldimethylsilyl, etc.), alkyldiarylsilyl (e.g., C₁₋₆ alkyl di-C₆₋₁₀ arylsilyl such as t-butyldiphenylsilyl, etc.), triaralkylsilyl (e.g., tribenzylsilyl, etc.), etc.

Examples of the acetal-type protective groups include alkoxyalkyl (e.g., C₁₋₄ alkoxy - C₁₋₄ alkyl such as methoxymethyl, 1-ethoxyethyl, 1-methyl-1-methoxyethyl, etc.), alkoxyalkoxyalkyl (e.g., C₁₋₄ alkoxy - C₁₋₄ alkoxy - C₁₋₄ alkyl such as methoxyethoxymethyl, etc.), alkylthioalkyl (e.g., C₁₋₄ alkylthio - C₁₋₄ alkyl such as methylthiomethyl, etc.), tetrahydropyranyl (e.g., tetrahydropyran-2-yl, 4-methoxytetrahydropyran-4-yl, etc.), tetrahydrothiopyranyl (e.g., tetrahydrothiopyran-2-yl, etc.), tetrahydrofuranyl (e.g., tetrahydrofuran-2-yl, etc.), tetrahydrothiofuranyl (e.g., tetrahydrothiofuran-2-yl, etc.), aralkyloxyalkyl (e.g., benzyloxymethyl, etc.), etc.

Of them, protective groups removable by acid treatment are preferred. In particular, tetrahydropyranyl (in this case, E is tetrahydropyranyloxy) and 1-ethoxyethyl (in this case, E is 1-ethoxyethoxy) are preferred, and tetrahydro-pyran-2-yl (in this case, E is 2-tetrahydropyranyloxy) is particularly preferred.

Examples of the acid to be used in this reaction include mineral acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, etc.; sulfonic acids such as p-toluenesulfonic acid, etc.; acid-base pairs such as pyridinium p-toluenesulfonate, etc.; etc. The amount of the acid to be used is 0.01 to 0.5 mol, preferably 0.05 to 0.2 mol, per mol of the compound (XXXV).

Examples of the solvent to be used include alcohols such as methanol, ethanol, etc.; aromatic hydrocarbons such as toluene, xylene, etc.; halogenated hydrocarbons such as methylene chloride, chloroform, etc.; ethers such as ether, tetrahydrofuran, etc.; and water. These solvents can be used alone or as a mixture thereof.

The reaction temperature is appropriately selected from the range of 0° C. to a reflux temperature of the solvent, and is preferably 20° C. to 80° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 12 hours.

The compound (XXXVI) thus obtained can be used in the next step as the reaction mixture or the crude product, or separating and purifying it by known methods (e.g., chromatography, recrystallization, etc.).

The compound (XXXV) which can be used as the starting material in this reaction can preferably be prepared by Method V described below.

Method V ##STR48## wherein L is a leaving group, and the other symbols are as defined above.

The compound (XXXV) can be prepared by reacting the compound (XXXII) with the compound (XXXIV) in an appropriate solvent in the presence of a base.

The leaving group represented by L in the above formula includes, for example, halogen atoms (e.g., chlorine, bromine, iodine, etc.), alkylsulfonyloxy (e.g., methanesulfonyloxy, etc.), arylsulfonyloxy, (e.g., p-toluenesulfonyloxy, etc.), etc.

Preferred examples of the compound (XXXIV) used in this reaction include alkyl halides (e.g., methyl chloride, methyl bromide, methyl iodide, ethyl chloride, ethyl bromide, ethyl iodide, 1-iodopropane, 2-iodopropane, 1-iodobutane, chlorotrifluoromethane, 1,2-dibromoethane, chloromethyl ether, etc.), alkenyl halides (e.g., allyl bromide, etc.), alkynyl halides (e.g., propargyl bromide, etc.), etc. The amount of the compound (XXXIV) to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (XXXII).

Examples of the base include organic bases (e.g., alkoxides such as sodium methoxide, sodium ethoxide, potassium t-butoxide, etc.), inorganic bases (e.g., metal hydroxides such as sodium hydroxide, potassium hydroxide, etc.; hydrides such as sodium hydride, potassium hydride, etc.), etc. The amount of the base to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (XXXII).

Examples of the solvent to be used include ethers such as diethyl ether, tetrahydrofuran, etc.; N,N-dimethylformamide, dimethyl sulfoxide, toluene, etc.

The reaction temperature is appropriately selected from the range of -20° C. to a reflux temperature of the solvent, and is preferably 0 to 50° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 10 hours.

The compound (XXXV) thus obtained can be used in the next step as the reaction mixture or the crude product, or after separating and purifying it by known methods (e.g., chromatography, recrystallization, etc.).

The compound (XXXII) which can be used as the starting material in this reaction can preferably be prepared by Method W described below.

Method W ##STR49## wherein each symbol is as defined above.

The compound (XXXII) can be prepared by reducing the compound (XXXI) in an appropriate solvent.

The reducing agent to be used is a conventional reducing agent for reduction of ketones, such as metal hydrides, metal hydride complex compounds, etc. Examples of the reducing agent include three-coordinate boranes (e.g., borane, etc.), four-coordinate borates (e.g., sodium borohydride, lithium borohydride, etc.), three-coordinate aluminiums (e.g., diisobutylaluminum hydride, etc.), four-coordinate alumininate complexes (e.g., lithium aluminum hydride, etc.), etc. The amount of the reducing agent to be used is 0.25 to 3 mol, preferably 1.0 to 1.2 mol, per mol of the compound (XXXI).

Examples of the solvent include alcohols such as methanol, ethanol, etc.; ethers such as diethyl ether, tetrahydofuran, etc.; water, etc. These solvents can be used alone or as a mixture thereof.

The reaction temperature is appropriately selected from the range of -20° C. to a reflux temperature of the solvent, and is preferably 0 to 50° C. The reaction time is 0.5 hour to 24 hours, preferably 0.5 to 2 hours.

The compound (XXXII) thus obtained can be used in the next step as the reaction mixture or the crude product, or after separating and purifying it by known methods (e.g., chromatography, recrystallization, etc.).

The compound (XXXI) used as the starting material in this reaction can be obtained by reacting a Grignard compound of 2-(substituted methyl)-1-bromobenzene with a dialkyl oxalate according to Journal of Organic Chemistry, USSR, Vol. 5, p. 1530 (1969).

The compound (XXXXI) included in the compound (XVIII) which can be used as the starting material in Method M can be prepared by Method X described below.

Method X ##STR50## wherein each symbol is as defined above.

The compound (XXXXI) can be prepared by reducing the compound (XXX) in an appropriate solvent.

The reducing agent to be used is a conventional reducing agent for reduction of ketones, such as metal hydrides, metal hydride complex compounds, etc. Examples of the reducing agent include three-coordinate boranes (e.g., borane, etc.), four-coordinate borates (e.g., sodium borohydride, lithium borohydride, etc.), three-coordinate aluminiums (e.g., diisobutylaluminum hydride, etc.), four-coordinate alumininate complexes (e.g., lithium aluminum hydride, etc.), etc. The amount of the reducing agent to be used is 0.25 to 3 mol, preferably 1.0 to 1.2 mol, per mol of the compound (XXX).

Examples of the solvent include alcohols such as methanol, ethanol, etc.; ethers such as diethyl ether, tetrahydofuran, etc.; water, etc. These solvents can be used alone or as a mixture thereof.

The reaction temperature is appropriately selected from the range of -20° C. to a reflux temperature of the solvent, and is preferably 0 to 50° C. The reaction time is 0.5 hour to 24 hours, preferably 0.5 to 2 hours.

The compound (XXXXI) thus obtained can be used in the next step as the reaction mixture or the crude product, or after separating and purifying it by known methods (e.g., chromatography, recrystallization, etc.).

The compound (XXXXIII) included in the compound (XVIII) which can be used as the starting material in Method M can preferably be prepared by Method Y described below.

Method Y ##STR51## wherein R⁹ is tetrahydropyranyl, and the other symbols are as defined above.

The compound (XXXXIII) can be prepared by introducing tetrahydropyranyl into the compound (XXXXI).

The tetrahydropyranyl represented by R⁹ includes, for example, 2-tetrahydropyranyl, etc.

The tetrahydropyranyl can be introduced by a conventional method for protecting hydroxyl with tetrahydropyranyl, for example, by reacting the compound (XXXXI) with dihydropyran in an appropriate solvent in the presence of an acid.

Examples of the acid include p-toluenesulfonic acid, hydrochloric acid, phosphorus oxychloride, acid-base pairs such as pyridinium p-toluenesulfonate, etc. The amount of the acid to be used is 0.01 to 0.5 mol, preferably 0.05 to 0.2 mol, per mol of the compound (XXXXI).

Examples of the solvent to be used include aromatic hydrocarbons such as toluene, xylene, etc.; halogenated hydrocarbons such as methylene chloride, chloroform, etc.; ethers such as ether, tetrahydrofuran, etc. These solvents can be used alone or as a mixture thereof.

The reaction temperature is appropriately selected from the range of 0° C. to a reflux temperature of the solvent, and is preferably 20° C. to 80° C. The reaction time is 0.5 hour to 48 hours, preferably 0.5 to 12 hours.

The compound (XXXXIII) thus obtained can be used in the next step as the reaction mixture or the crude product, or separating and purifying it by known methods (e.g., chromatography, recrystallization, etc.).

The compound (XXXXI) which can be used as the starting material in this reaction can preferably be prepared by Method X described above.

The compound (XXXXV) included in the compound (XXIII) which can be used as the starting material in Method N can be prepared by Method Z described below.

Method Z ##STR52## wherein R¹⁰ is optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl, D is a halogen atom, M¹ is a sulfur atom or NR² (R² is a hydrogen atom, alkyl or acyl), and the other symbols are as defined above.

The compound (XXXXV) can be prepared by reacting the compound (XXXXIV) with the compound (XXIX).

The compound (XXIX) may be in the form of a metal salt. Examples of the metal salt include alkaline metal salts (sodium salt, potassium salt, etc.), alkaline earth metal salts (magnesium salt, calcium salt, etc.), etc.

When a metal salt of a mercaptan such as hydrogen sulfide (e.g., sodium hydrosulfide, potassium hydrosulfide) is used as the compound (XXIX), the amount of it to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (XXXXIV) . Examples of the solvent include alcohols such as methanol, ethanol, etc.; halogenated hydrocarbons such as methylene chloride, 1,2-dichloroethane, etc.; ethers such as diethyl ether, etc.; aromatic hydrocarbons such as toluene, etc., dimethyl sulfoxide, N,N-dimethylformamide, etc. The reaction temperature is appropriately selected from the range of 0° C. to a reflux temperature of the solvent, preferably room temperature to a reflux temperature of the solvent. The reaction time is 0.5 hour to 24 hours, preferably 1 to 5 hours.

When an amine or a metal salt of an amine (e.g., sodium amide, etc.) is used as the compound (XXIX), the amount of it to be used is 1 to 5 mol, preferably 1 to 2 mol, per mol of the compound (XXXXIV). Examples of the solvent include alcohols such as methanol, ethanol, etc.; halogenated hydrocarbons such as methylene chloride, 1,2-dichloroethane, etc.; ethers such as diethyl ether, etc.; aromatic hydrocarbons such as toluene, etc., dimethyl sulfoxide, N,N-dimethylformamide, etc.

The reaction temperature is appropriately selected from the range of 0° C. to a reflux temperature of the solvent, and is preferably 0° C. to room temperature. The reaction time is 0.5 hour to 24 hours, preferably 1 to 5 hours.

The compound (XXXXV) thus obtained can be used in the next step as the reaction mixture or the crude product, or after separating and purifying it by known methods (e.g., chromatography, recrystallization, etc.).

The compound of the formula (I) of the present invention is effective against a wide variety of phytopathogenic fungi on crop plants (e.g., rice, wheat, barley, rye, corn, common millet, millet, buckwheat, soybean, redbean, peanut, etc.), fruit trees (e.g., citrus fruits, grape, apple, pear, peach, etc.), vegetables (e.g., cucumber, eggplant, tomato, pumpkin, kidney bean, etc.), etc., or seeds thereof. It is also effective against phytopathogenic fungi in soil. The compound of the present invention shows potent fungicidal activity particularly against Pyricularia oryzae, Rhizoctonia solani, Erysiphe graminis, Sphaerotheca fuliginea, Erysiphe cichoracearum, Phylophthora infestans, Pseudoperonospora cubensis, Peronospora manshurica, Plasaopara viticola, Botrytis cinerea of vegetables, grape, etc., Pythium aphanidermatum, Sclerotinia sclerotiorum of buckwheat, soybean, colza, etc., Corticium rolfsii of soybean, redbean, potato, peanut, etc., Pseudocercosporella herpotrichoides, Puccinia coronata, etc. Therefore, the compound (I) of the present invention is useful as agricultural fungicides.

Application of the compound (I) of the present invention may be made to plants by any conventional procedure such as atomizing, scattering or spreading of the active compound. Application may also be made by treating with the active compound seeds of plants, soil where plants grow, soil for seeding, paddy field or water for perfusion. Application may be performed before or after the infection with phytopathogenic fungi on plants.

The compound can be used in a conventional formulation form suitable for agricultural fungicides such as solutions, wettable powders, emulsions, suspensions, concentrated liquid preparations, tablets, granules, aerosols, powders, pastes, dusts, etc.

Such formulation form can be prepared in a conventional manner by mixing at least one compound of the present invention with an appropriate solid or liquid carrier(s) and, if necessary, an appropriate adjuvant(s) (e.g., surfactants, spreaders, dispersants, stabilizers, etc.) for improving the dispersibility and other properties of the active compound.

Examples of the solid carriers or diluents include botanical materials (e.g., flour, tobacco stalk powder, soybean powder, walnut-shell powder, vegetable powder, saw dust, bran, bark powder, cellulose powder, vegetable extract residue, etc.), fibrous materials (e.g., paper, corrugated cardboard, old rags, etc.), artificial plastic powders, clays (e.g., kaolin, bentonite, fuller's earth, etc.), talc, other inorganic materials (e.g., pyrophyllite, sericite, pumice, sulfur powder, active carbon, etc.), chemical fertilizers (e.g., ammonium sulfate, ammonium phosphate, ammonium nitrate, urea, ammonium chloride, etc.), etc.

Examples of the liquid carriers or diluents include water, alcohols (e.g., methanol, ethanol, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), ethers (e.g., diethyl ether, dioxane, cellosolve, tetrahydrofuran, etc.), aromatic hydrocarbons (e.g., benzene, toluene, xylene, methylnaphthalene, etc.), aliphatic hydrocarbons (e.g., gasoline, kerosene, lamp oil, etc.), esters, nitrites, acid amides (e.g., dimethylformamide, dimethylacetamide, etc.), halogenated hydrocarbons (e.g., dichloroethane, carbon tetrachloride, etc.), etc.

Examples of the surfactants include alkyl sulfates, alkyl sulfonates, alkylaryl sulfonates, polyethylene glycol ethers, polyhydric alcohol esters, etc.

Examples of the spreaders or dispersants include casein, gelatin, starch powder, carboxymethyl cellulose, gum arabic, alginic acid, lignin, bentonite, molasses, polyvinyl alcohol, pine oil, agar, etc.

Examples of the stabilizers include PAP (a mixture of isopropylphosphate), tricresyl phosphate (TCP), tolu oil, epoxidized oil, surfactants, fatty acids and their esters, etc.

The composition of the present invention may contain other fungicides, insecticides, herbicides or fertilizers in addition to the above ingredients.

In general, the above composition contains at least one compound of the formula (I) of the present invention in a concentration of 1 to 95% by weight, preferably 2.0 to 80% by weight. The composition can be used as such or in a diluted form. About 1.0 g to 5 kg/hectare, preferably about 2 g to 100 g/hectare, of the compound of the present invention is used in a concentration of normally about 1 to 50,000 ppm, preferably about 100 to 5,000 ppm.

EXAMPLES

The following examples and test examples further illustrate the present invention in detail, but are not to be construed to limit the scope thereof. The coupling constants (J) are indicated in hertz (Hz).

Example 1 Synthesis of 2-hydroxy-2-(2-phenoxyphenyl)acetamide (Compound No. 2)

2-Oxo-2-(2-phenoxyphenyl)acetamide (4.82 g, 20.0 mmol) was dissolved in ethanol (50 ml). Sodium borohydride (0.76 g, 20.0 mmol) was added slowly under ice-cooling. After stirring for 30 minutes, the mixture was neutralized with 1N hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate, and the solvent was evaporated to give an oil. The oil was purified by column chromatography on silica gel (eluting with n-hexane - ethyl acetate) to give the desired compound 2-hydroxy-2-(2-phenoxyphenyl)acetamide (4.3 g, 89%) as colorless crystals. The compound was recrystallized from a mixed solvent of n-hexane - methylene chloride to give colorless crystals.

mp.: 121-122° C.

NMR (δ ppm TMS/CDCl₃): 4.11(1H,brs), 5.46(1H,s), 5.57(1H,brs), 6.58(1H,brs), 6.88(1H,dd,J=7.9,1.2), 7.03 (2H,dd,J=7.9,1.2), 7.13-7.20(2H,m), 7.23-7.27(1H,m), 7.29-7.40(2H,m), 7.58(1H,dd,J=7.9,1.2).

Example 2 Synthesis of 2- 2-(2,5-dimethylphenoxymethyl)-phenyl!-2-hydroxy-N-methylacetamide (Compound No. 75)

2- 2-(2,5-Dimethylphenoxymethyl)phenyl!-N-methyl-2-oxoacetamide (0.93 g, 3.1 mmol) was dissolved in methanol (10 ml). Sodium borohydride (0.06 g, 1.6 mmol) was added slowly under ice-cooling. After stirring for 30 minutes, the mixture was neutralized with 1N hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate, and the solvent was evaporated to give an oil. The oil was purified by column chromatography on silica gel (eluting with n-hexane - ethyl acetate) to give the desired compound 2- 2-(2,5-dimethylphenoxymethyl)phenyl!-2-hydroxy-N-methylacetamide (0.85 g, 91%) as white crystals.

mp.: 86-87° C.

NMR (δ ppm TMS/CDCl₃) : 2.16(3H,s) , 2.35(3H,s) 2.78(3H,d,J=4.9), 4.35(1H,d,J=3.7), 4.94(1H,d,J=11.0), 5.34(1H,d,J=11.0), 5.35(1H,d,J=3.7), 6.49(1H,brs), 6.78 (1H,d,J=7.3), 6.87(1H,s), 7.06(1H,d,J=7.3), 7.32-7.48(4H,m).

Example 3

According to the same manner as that described in Example 1 or 2, the compounds of the formula (I-7) were synthesized. The compounds thus obtained and the physical data of their representative compounds are as follows. ##STR53##

    __________________________________________________________________________     Comp. No.                                                                          1                   Y     Property                                                                            mp or .sup.1 H-NMR(CDCl.sub.3) δ                                         ppm                                         __________________________________________________________________________      1                                                                                 2 #STR54##          NHCH.sub.3                                                                           crystal                                                                             99.0˜99.5° C.                   2                                                                                 2 #STR55##          NH.sub.2                                                                             crystal                                                                             121˜122° C.                     3                                                                                 2 #STR56##          N(CH.sub.3).sub.2                                                                    crystal                                                                             127˜128° C.                     4                                                                                 2 #STR57##          NHCH.sub.2 OH                                                                        crystal                                                                             94.5˜95.5° C.                   5                                                                                 3 #STR58##          NHCH.sub.3                                              6                                                                                 4 #STR59##          NH.sub.2                                                7                                                                                 4 #STR60##          NHCH.sub.3                                                                           oil  2.34(3H, s), 2.81(3H, d, J= 4.9),                                              4.20(1H, br), 5.40 (1H, s), 6.4(1H,                                            brs), 6.80-6.88(3H, m), 6.96(1H, d,                                            J=7.3), 7.13-7.28(3H, m), 7.55(1H, dd,                                         J= 7.3, 1.8).                                8                                                                                 4 #STR61##          NHCH.sub.2 OH                                           9                                                                                 4 #STR62##          N(CH.sub.3).sub.2                                      10                                                                                 5 #STR63##          NH.sub.2                                               11                                                                                 5 #STR64##          NHCH.sub.3                                                                           crystal                                                                             79˜82° C.                      12                                                                                 5 #STR65##          NHCH.sub.2 OH                                          13                                                                                 5 #STR66##          N(CH.sub.3).sub.2                                      14                                                                                 5 #STR67##          NHC.sub.2 H.sub.5                                      15                                                                                 6 #STR68##          NHCH.sub.3                                                                           oil  2.25(6H, s), 2.84(3H, d, J= 4.9),                                              5.43(1H, s), 6.58(1H, brs), 6.74(1H,                                           dd, J=7.3, 1.2), 6.81(1H, s), 6.83(1H,                                         d, J=7.3), 7.11(1H, d, J=7.3),                                                 7.13(1H, dt, J=1.2, 7.3), 7.22(1H, dt,                                         J=1.8, 7.3), 7.54(1H, dd, J=7.3,                                               1.8).                                       16                                                                                 7 #STR69##          NHCH.sub.3                                                                           crystal                                                                             119˜120° C.                    17                                                                                 8 #STR70##          NHCH.sub.3                                             18                                                                                 9 #STR71##          NHCH.sub.3                                             19                                                                                 0 #STR72##          NHCH.sub.3                                             20                                                                                 1 #STR73##          NHCH.sub.3                                             21                                                                                 2 #STR74##          NHCH.sub.3                                             22                                                                                 3 #STR75##          NH.sub.2                                               23                                                                                 3 #STR76##          NHCH.sub.3                                                                           oil  2.83(3H, d, J=4.9), 4.20 (1H, brs),                                            5.36(1H, s), 6.41(1H, brs), 6.84(1H,                                           d, J=6.7), 6.93-6.98(2H, m),                                                   7.16-7.33(4H, m), 7.53(1H, dd, J=7.3,                                          1.8).                                       24                                                                                 3 #STR77##          NHCH.sub.2 OH                                          25                                                                                 3 #STR78##          N(CH.sub.3).sub.2                                      26                                                                                 3 #STR79##          NHC.sub.2 H.sub.5                                      27                                                                                 4 #STR80##          NHCH.sub.3                                             28                                                                                 5 #STR81##          NHCH.sub.3                                             29                                                                                 6 #STR82##          NHCH.sub.3                                             30                                                                                 7 #STR83##          NHCH.sub.3                                             31                                                                                 8 #STR84##          NHCH.sub.3                                             32                                                                                 9 #STR85##          NHCH.sub.3                                             33                                                                                 0 #STR86##          NHCH.sub.3                                             34                                                                                 1 #STR87##          NHCH.sub.3                                             35                                                                                 2 #STR88##          NHCH.sub.3                                             36                                                                                 3 #STR89##          NHCH.sub.3                                             37                                                                                 4 #STR90##          NHCH.sub.3                                             38                                                                                 5 #STR91##          NHCH.sub.3                                             39                                                                                 6 #STR92##          NHCH.sub.3                                             40                                                                                 7 #STR93##          NHCH.sub.3                                             41                                                                                 8 #STR94##          NHCH.sub.3                                             42                                                                                 9 #STR95##          NHCH.sub.3                                             43                                                                                 0 #STR96##          NHCH.sub.3                                             44                                                                                 1 #STR97##          NHCH.sub.3                                             45                                                                                 9 #STR98##          NHCH.sub.3                                             46                                                                                 2 #STR99##          NHCH.sub.3                                                                           oil  2.34(3H, s), 2.83(3H, d, J= 4.9),                                              4.20(1H, brs), 5.36 (1H, s), 6.41(1H,                                          brs), 6.76- 6.90(3H, m), 7.17-7.31(3H,                                         m), 7.56(1H, dd, J=7.3, 1.8).               47                                                                                 3 #STR100##         NHCH.sub.3                                             48                                                                                 4 #STR101##         NHCH.sub.3                                             49                                                                                 5 #STR102##         NHCH.sub.3                                             50                                                                                 6 #STR103##         NHCH.sub.3                                             51                                                                                 7 #STR104##         NHCH.sub.3                                             52                                                                                 8 #STR105##         NHCH.sub.3                                             53                                                                                 9 #STR106##         NHCH.sub.3                                             54                                                                                 0 #STR107##         NHCH.sub.3                                             55                                                                                 1 #STR108##         NHCH.sub.3                                             56                                                                                 2 #STR109##         NHCH.sub.3                                             57                                                                                 3 #STR110##         NHCH.sub.3                                             58                                                                                 4 #STR111##         NHCH.sub.3                                             59                                                                                 5 #STR112##         NHCH.sub.3                                             60                                                                                 6 #STR113##         NHCH.sub.3                                             61                                                                                 7 #STR114##         NHCH.sub.3                                             62                                                                                 8 #STR115##         NH.sub.2                                               63                                                                                 8 #STR116##         NHCH.sub.3                                                                           oil  2.81(3H, d, J=4.9), 5.02(1H, d,                                                J=11.0), 5.26(1H, s), 5.30(1H, d,                                              J=11.0), 6.73(1H, brs), 6.97(2H, d,                                            J=7.9), 7.05 (1H, t, J=7.3), 7.31-7.50                                         (6H, m)                                     64                                                                                 9 #STR117##         NHCH.sub.3                                                                           crystal                                                                             104.6˜105.7° C.                65                                                                                 9 #STR118##         NH.sub.2                                               66                                                                                 9 #STR119##         NHCH.sub.2 OH                                          67                                                                                 9 #STR120##         N(CH.sub.3).sub.2                                      68                                                                                 9 #STR121##         NHC.sub.2 H.sub.5                                      69                                                                                 0 #STR122##         NHCH.sub.3                                                                           oil  2.36(3H, s), 2.75(3H, d, J=4.8),                                               4.55(1H, brs), 4.97 (1H, d, J=11.0),                                           5.20(1H, s), 5.21(1H, d, J=11.0),                                              6.73-6.84(4H, m), 7.19(1H, t, J=7.6),                                          7.28- 7.44(4H, m)                           70                                                                                 1 #STR123##         NHCH.sub.3                                                                           oil  2.30(3H, s), 2.77(3H, d, J=4.8),                                               4.55(1H, m), 4.97 (1H, d, J=11.0),                                             5.23(1H, s), 5.24(1H, d, J=11.0),                                              6.83(1H, brs), 6.85(2H, d, J=8.8),                                             7.13(2H, d, J=8.8), 7.29-7.48(4H, m)        71                                                                                 2 #STR124##         NHCH.sub.3                                                                           oil  2.76(3H, d, J=4.8), 4.60(1H, brs),                                             5.11(1H, d, J=11.0), 5.12(1H, s), 5.16                                         (1H, d, J=11.0), 6.61(1H, brs),                                                7.09-7.18(2H, m), 7.27-7.44(6H, m)          72                                                                                 3 #STR125##         NHCH.sub.3                                             73                                                                                 4 #STR126##         NHCH.sub.3                                             74                                                                                 5 #STR127##         NH.sub.2                                                                             oil  2.12(3H, s), 2.33(3H, s), 4.40 (1H, d,                                         J=4.3), 4.93(1H, d, J=11.0), 5.27(1H,                                          d, J=11.0), 5.34(1H, d, J=4.3),                                                6.06(1H, brs), 6.63(1H, brs), 6.75(1H,                                         d, J=7.3), 6.83(1H, s), 7.03(1H, d,                                            J=7.9), 7.29-7.47(4H, m).                   75                                                                                 5 #STR128##         NHCH.sub.3                                                                           crystal                                                                             86˜87° C.                      76                                                                                 5 #STR129##         NHCH.sub.2 OH                                          77                                                                                 5 #STR130##         N(CH.sub.3).sub.2                                                                    crystal                                                                             144˜145° C.                    78                                                                                 5 #STR131##         NHC.sub.2 H.sub.5                                                                    oil  0.99(3H, d, J=7.3), 2.17(3H, s),                                               2.32(3H, s), 3.13-3.27(2H, m),                                                 4.45(1H, d, J=4.3), 4.96 (1H, d,                                               J=11.6), 5.24(1H, d, J=11.6), 5.28(1H,                                         d, J=4.3), 6.62(1H, brs).                   79                                                                                 6 #STR132##         NHCH.sub.3                                             80                                                                                 7 #STR133##         NHCH.sub.3                                             81                                                                                 8 #STR134##         NHCH.sub.3                                             82                                                                                 9 #STR135##         NHCH.sub.3                                             83                                                                                 0 #STR136##         NHCH.sub.3                                             84                                                                                 1 #STR137##         NH.sub.2                                               85                                                                                 1 #STR138##         NHCH.sub.3                                                                           oil  2.80(3H, d, J=4.9), 4.99(1H, d,                                                J=10.4), 5.28(1H, s), 5.42(1H, d,                                              J=10.4), 6.62 (1H, brs), 7.00(1H, t,                                           J=7.3), 7.16(1H, d, J=7.9),                                                    7.28-7.50(6H, m)                            86                                                                                 1 #STR139##         NHCH.sub.2 OH                                          87                                                                                 1 #STR140##         N(CH.sub.3).sub.2                                      88                                                                                 1 #STR141##         NHC.sub.2 H.sub.5                                      89                                                                                 2 #STR142##         NHCH.sub.3                                             90                                                                                 3 #STR143##         NH.sub.2                                               91                                                                                 3 #STR144##         NHCH.sub.3                                                                           crystal                                                                             68˜70° C.                      92                                                                                 3 #STR145##         NHCH.sub.2 OH                                          93                                                                                 3 #STR146##         N(CH.sub.3).sub.2                                      94                                                                                 3 #STR147##         NHC.sub.2 H.sub.5                                      95                                                                                 4 #STR148##         NHCH.sub.3                                             96                                                                                 5 #STR149##         NHCH.sub.3                                             97                                                                                 6 #STR150##         NHCH.sub.3                                             98                                                                                 7 #STR151##         NHCH.sub.3                                             99                                                                                 8 #STR152##         NHCH.sub.3                                                                           oil  2.80(3H, d, J=4.9), 5.00(1H, d,                                                J=11.0), 5.26(1H, s), 5.38(1H, d,                                              J=11.0), 6.50(1H, brs), 7.07(1H, d,                                            J=8.5), 7.25- 7.29(1H, m), 7.31-7.50                                           (5H, m)                                     100                                                                                9 #STR153##         NHCH.sub.3                                             101                                                                                0 #STR154##         NHCH.sub.3                                             102                                                                                1 #STR155##         NHCH.sub.3                                             103                                                                                2 #STR156##         NHCH.sub.3                                             104                                                                                3 #STR157##         NHCH.sub.3                                                                           oil  2.76(3H, d, J=4.8), 3.76(3H, s),                                               4.50(1H, brs), 4.95(1H, d, J=11.0),                                            5.19(1H, d, J=11.0) 5.24(1H, s),                                               6.83-6.88(5H, m), 7.30-7.43(4H, m)          105                                                                                4 #STR158##         NHCH.sub.3                                             106                                                                                5 #STR159##         NHCH.sub.3                                             107                                                                                6 #STR160##         NHCH.sub.3                                             108                                                                                7 #STR161##         NHCH.sub.3                                             109                                                                                8 #STR162##         NHCH.sub.3                                             110                                                                                9 #STR163##         NHCH.sub.3                                             111                                                                                0 #STR164##         NHCH.sub.3                                             112                                                                                1 #STR165##         NH.sub.2                                                                             crystal                                                                             151˜152° C.                    113                                                                                1 #STR166##         NHCH.sub.3                                                                           crystal                                                                             142˜143° C.                    114                                                                                1 #STR167##         NHCH.sub.2 OH                                          115                                                                                1 #STR168##         N(CH.sub.3).sub.2                                                                    crystal                                                                             125˜127° C.                    116                                                                                1 #STR169##         NHC.sub.2 H.sub.5                                                                    oil  0.99-1.17(3H in total), 2.19(3H, s),                                           3.15-3.31(2H in total), 4.48(1H, br),                                          5.02(1H, d, J=11.8), 5.18 (1H, d,                                              J=11.6), 5.21(1H, s), 6.61(1H, brs),                                           6.83(1H, d, J=8.5), 7.08(1H, d, J=                                             8.5), 7.12(1H, s), 7.31- 7.43(4H, m).       117                                                                                2 #STR170##         NHCH.sub.3                                             118                                                                                3 #STR171##         NHCH.sub.3                                             119                                                                                4 #STR172##         NHCH.sub.3                                             120                                                                                5 #STR173##         NHCH.sub.3                                             121                                                                                6 #STR174##         NHCH.sub.3                                             122                                                                                7 #STR175##         NHCH.sub.3                                             123                                                                                8 #STR176##         NHCH.sub.3                                             124                                                                                9 #STR177##         NHCH.sub.3                                             125                                                                                0 #STR178##         NHCH.sub.3                                             126                                                                                1 #STR179##         NHCH.sub.3                                             127                                                                                2 #STR180##         NHCH.sub.3                                             128                                                                                3 #STR181##         NHCH.sub.3                                             129                                                                                4 #STR182##         NHCH.sub.3                                             130                                                                                5 #STR183##         NHCH.sub.3                                             131                                                                                6 #STR184##         NHCH.sub.3                                             132                                                                                7 #STR185##         NHCH.sub.3                                             133                                                                                8 #STR186##         NHCH.sub.3                                             134                                                                                6 #STR187##         NH.sub.2                                               135                                                                                6 #STR188##         NHCH.sub.2 OH                                          136                                                                                7 #STR189##         NH.sub.2                                               137                                                                                7 #STR190##         NHCH.sub.2 OH                                          __________________________________________________________________________

Example 4 Synthesis of methyl 2- 2-(2,5-dimethylphenoxymethyl)phenyl!2-methoxyacetate (Compound No. 139)

60% oily sodium hydride (0.13 g, 3.3 mmol) was added to a solution of methyl 2- 2-(2,5-dimethylphenoxymethyl)-phenyl!-2hydroxyacetate (0.72 g, 2.4 mmol) and methyl iodide (0.68 g, 4.8 mmol) in N,N-dimethylformamide (6 ml) at 0° C. with stirring. After 30 minutes, ice and water were added in this order, and the mixture was extracted with ethyl acetate, washed successively with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=9/1) to give the desired compound methyl 2- 2-(2,5-dimethylphenoxymethyl)phenyl!-2-hydroxyacetate (0.69 g, 92%) as an oil.

NMR (δ ppm, TMS/CDCl₃): 2.21(3H,s), 2.33(3H,s), 3.40 (3H,s), 3.70(3H,s), 5.10(1H,d,J=12.2), 5.14(1H,s), 5.28 (1H,d,J=12.2), 6.71(1H,d,J=7.3), 6.76(1H,s), 7.04(1H,d,J=7.3), 7.33-7.40(2H,m), 7.50-7.56(2H,m).

Example 5 Synthesis of 2- 2-(2,5-dimethylphenoxymethyl)phenyl!-2-methoxy-N-methylacetamide (Compound No. 140)

A solution of methyl 2- 2-(2,5-dimethylphenoxymethyl)phenyl!-2-methoxyacetate (0.44 g, 1.40 mmol) in methanol (5 ml) was stirred at room temperature. 40% methylamine/methanol solution (0.33 g, 4.2 mmol) was added thereto. After 22 hours, the mixture was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=2/1) to give the desired compound 2- 2-(2,5-dimethylphenoxymethyl)phenyl!-2-methoxy-N-methylacetamide (0.36 g, 82%) as white crystals.

mp: 86-88° C.

NMR (δ ppm, TMS/CDCl₃): 2.19(3H,s), 2.32(3H,s), 2.83 (3H,d,J=4.9), 3.36(3H,s), 5.04(1H,s), 5.07(1H,d,J=11.6), 5.47 (1H,d,J=11.6), 6.70(1H,d,J=7.3), 6.79(1H,brs), 6.79(1H,s), 7.03(1H,d,J=7.9), 7.33-7.43(3H,m), 7.49-7.54(1H,m).

Example 6 Synthesis of 2- 2-(2,5-dimethylphenoxymethyl)phenyl!-2-methoxy-N-methylthioacetamide (Compound No. 170)

A solution of 2- 2-(2,5-dimethylphenoxymethyl)phenyl!-2-methoxy-N-methylacetamide (0.12 g, 0.38 mmol) and Lawesson's reagent (0.14 g, 0.35 mmol) in toluene (5 ml) was heated with stirring at 80° C. for 2 hours. The mixture was cooled to room temperature, and purified by column chromatography on silica gel (n-hexane/ethyl acetate=4/1) to give the desired compound 2- 2-(2,5-dimethylphenoxymethyl)-phenyl!-2-methoxy-N-methylthioacetamide (0.13 g, 100%) as an oil.

NMR (δ ppm TMS/CDCl₃): 2.20(3H,s), 2.32(3H,s), 3.23 (3H,d,J=4.8), 3.35(3H,s), 5.12(1H,d,J=11.6), 5.40(1H,s), 5.58 (1H,d,J=11.6), 6.70(1H,d,J=7.3), 6.81(1H,s), 7.03(1H,d,J=7.3), 7.28-7.38(3H,m), 7.48-7.52(1H,m), 8.78(1H,brs).

Example 7 Synthesis of 2-acetoxy-2- 2-(2,5-dimethylphenoxymethyl)phenyl!-2-N-methylacetamide (Compound No. 144)

A solution of 2- 2-(2,5-dimethylphenoxymethyl)-phenyl!-2-hydroxy-N-methylacetamide (0.57 g, 1.9 mmol) and acetic anhydride (0.43 g, 4.2 mmol) in pyridine (3 ml) was stirred at room temperature for 8 hours, and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=1/1) to give the desired compound 2-acetoxy-2- 2-(2,5-dimethylphenoxymethyl)phenyl!-N-methylacetamide (0.53 g, 82%) as colorless crystals.

mp.: 114-115° C.

NMR (δ ppm TMS/CDCl₃): 2.18(3H,s), 2.19(3H,s), 2.34 (3H,s), 2.76(3H,d,J=4.9), 5.02(1H,d,J=11.6), 5.45 (1H,d,J=11.6), 6.19(1H,brs), 6.35(1H,s), 6.75(1H,d,J=7.3), 6.85(1H,s), 7.05(1H,d,J=7.3), 7.36-7.58(4H,m).

Example 8 Synthesis of methyl 2-chloro-2- 2-(2,5-dimethylphenoxymethyl)phenyl!acetate (Compound No. 149)

A solution of methyl 2- 2-(2,5-dimethylphenoxymethyl)phenyl!-2-hydroxyacetate (0.50 g, 1.6 mmol) in 1,2-dichloroethane (20 ml) was stirred at room temperature. Thionyl chloride (0.61 g, 5.1 mmol) was added thereto, and the mixture was heated under reflux overnight and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=97/3) to give the desired compound methyl 2-chloro-2- 2-(2,5-dimethylphenoxymethyl)phenyl!acetate (0.35 g, 66%) as an oil.

NMR (δ ppm TMS/CDCl₃): 2.20(3H,s), 2.35(3H,s), 3.76 (3H,s), 5.14(2H,s), 5.84(1H,s), 6.73(1H,d,J=7.3), 6.77(1H,s), 7.05(1H,d,J=7.3), 7.38-7.48(3H,m), 7.66(1H,d,J=7.3).

Example 9 Synthesis of methyl 2- 2-(2,5-dimethylphenoxymethyl)phenyl!-2-nitroacetate (Compound No. 439)

A solution of methyl 2-chloro-2- 2-(2,5-dimethylphenoxymethyl)phenyl!acetate (0.35 g, 1.1 mmol), sodium nitrite (0.13 g, 1.9 mmol) and phloroglucinol (0.145 g, 1.1 mol) in N,N-dimethylformamide (10 ml) was stirred at room temperature for 6 hours. Water was added to the mixture. The resulting mixture was extracted with ether, washed successively with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane/methylene chloride=1/1) to give the desired compound methyl 2- 2-(2,5-dimethylphenoxymethyl)phenyl!-2-nitroacetate (0.08 g, 22%) as an oil.

NMR (δ ppm, TMS/CDCl₃) : 2.09(3H,s) , 2.34(3H,s) 3.85 (3H,s), 5.05(1H,d,J=11.0), 5.10(1H,d,J=11.0), 6.68(1H,s), 6.74 (1H,d,J=7.3), 6.75(1H,s), 7.03(1H,d,J=7.3), 7.48-7.53(2H,m), 7.61-7.66(1H,m).

Example 10 Synthesis of methyl 2- 2-(2,5-dimethylphenoxymethyl)phenyl!-2-methylthioacetate (Compound No. 162)

A solution of methyl 2-chloro-2- 2-(2,5-dimethylphenoxymethyl)phenyl!acetate (0.21 g, 0.66 mmol) and sodium thiomethoxide (0.06 g, 0.86 mmol) in N,N-dimethylformamide (3 ml) was stirred at room temperature for 24 hours. Water was added, and the mixture was extracted with ether, washed successively with water and saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=9/1) to give the desired compound methyl 2- 2-(2,5-dimethylphenoxymethyl)phenyl!-2-thiomethyl-acetate (0.13 g, 60%) as an oil.

NMR (δ ppm, TMS/CDCl₃) : 2.10(3H,s), 2.20(3H,s) 2.34 (3H,s), 3.71(3H,s), 4.95(1H,s), 5.13(2H,s), 6.72(1H,d,J=7.3), 6.77(1H,s), 7.04(1H,d,J=7.3), 7.30-7.40 (2H,m), 7.46 (1H,dd,J=7.3,1.8), 7.68(1H,dd,J=7.3,1.8).

Example 11 Synthesis of methyl 2- 2-(2,5-dimethylphenoxymethyl)phenyl!-2-methylsulfinylacetate (Compound No. 358) and methyl 2- 2-(2,5-dimethylphenoxymethyl)phenyl!-2-methylsulfonylacetate (Compound No. 359)

A solution of methyl 2- 2-(2,5-dimethylphenoxymethyl)phenyl!-2-methylthioacetate (0.13 g, 0.39 mmol) in methylene chloride (5 ml) was stirred at 0° C. 80% m-chloroperbenzoic acid (0.12 g, 0.56 mmol) was added thereto. The mixture was stirred at 0° C. for 2 hours, washed with aqueous sodium thiosulfate solution, 1N sodium hydroxide solution and dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=3/1 followed by 1/1) to give the desired compound methyl 2- 2-(2,5-dimethylphenoxymethyl)phenyl!-2-methylsulfonylacetate (0.08 g, 56%) as crystals and methyl 2- 2-(2,5-dimethylphenoxymethyl)phenyl!-2-methylsulfinylacetate (0.03 g, 22%) as an oil.

Compound No. 359; mp. 122-124° C.

NMR (δ ppm TMS/CDCl₃): 2.17(3H,s), 2.34(3H,s), 3.03 (3H,s), 3.81(3H,s), 5.02(1H,d,J=11.6), 5.39(1H,d,J=11.6), 5.67 (1H,s), 6.72(1H,d,J=7.3), 6.79(1H,s), 7.03(1H,d,J=7.3), 7.40-7.55(3H,m), 7.81-7.85(1H,m).

Compound No. 358;. NMR (5 ppm, TMS/CDCl₃): 2.17 (3H,s), 2.34 and 2.36 (3H in total), 2.44 and 2.63 (3H in total), 3.78 and 3.81 (3H in total), 4.98-5.22 (3H in total), 6.71-7.81(7H in total).

Example 12 Synthesis of 2- 2-(2,5-dimethylphenoxymethyl)-phenyl!butyronitrile

A solution of 2- 2-(2,5-dimethylphenoxymethyl)-phenyl!acetonitrile (2.00 g, 8.0 mmol) in N,N-dimethyl-formamide (20 ml) was stirred at 0° C. 60% oily sodium hydride (0.38 g, 9.5 mmol) was added thereto, and then ethyl iodide (1.37 g, 8.8 mmol) was added dropwise over 5 minutes. After 1 hour, water was added, and the mixture was extracted with ethyl acetate, washed successively with water and saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=19/1) to give the desired compound 2- 2-(2,5-dimethylphenoxymethyl)phenyl!butyronitrile (1.91 g, 86%) as an oil.

NMR (δ ppm TMS/CDCl₃): 1.10(3H,t,J=7.3), 1.97 (2H,quintet,J=7.3), 2.16(3H,s), 2.34(3H,s), 4.05(1H,t,J=7.3), 4.96(1H,d,J=11.0), 5.05(1H,d,J=11.0), 6.73(1H,d,J=7.3), 6.76 (1H,s), 7.04(1H,d,J=7.3), 7.31-7.44(3H,m), 7.55(1H,d,J=7.9).

Example 13 Synthesis of 2- 2-(2,5-dimethylphenoxymethyl)-phenyl!butylamide (Compound No. 159)

A solution of 2- 2-(2,5-dimethylphenoxymethyl)-phenyl!butyronitrile (1.00 g, 3.6 mmol) and 96% sodium hydroxide (0.44 g, 10.6 mmol) in methanol (10 ml) was heated under reflux for 44 hours. The solvent was evaporated, and then water was added. The mixture was extracted with ethyl acetate, washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=3/1) to give the desired compound 2- 2-(2,5-dimethylphenoxymethyl)phenyl!butylamide (0.28 g, 26%) as white crystals.

mp.: 100-101° C.

NMR (δ ppm TMS/CDCl₃): 0.89(3H,t,J=7.3), 1.78-1.89(1H,m), 2.15(3H,s), 2.15-2.28(1H,m), 2.36(3H,s), 3.73 (1H,t,J=7.3), 4.84(1H,d,J=11.0), 5.20(1H,brs), 5.26 (1H,d,J=11.0), 5.86(1H,brs), 6.77(1H,d,J=7.3), 7.30 (1H,d,J=7.3), 7.38-7.43(2H,m), 7.49(1H,d,J=7.3).

Example 14 Synthesis of 2- 2-(2,5-dimethylphenoxymethyl)-phenyl!-N-methylbutylamide (Compound No. 146) and N,N-dimethyl-2- 2-(2,5-dimethylphenoxymethyl)phenyl!butylamide (Compound No. 163)

2- 2-(2,5-Dimethylphenoxymethyl)phenyl!butylamide (0.19 g, 0.6 mmol) was dissolved in N,N-dimethylformamide (5 ml), and the solution was stirred at 0° C. 60% oily sodium hydride (0.05 g, 1.3 mmol) was added thereto. After 5 minutes, methyl iodide (0.18 g, 1.3 mmol) was added, and then the mixture was stirred at room temperature for 2 hours. Ice and water were added in this order at 0° C., and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=4/1 followed by 3/1) to give the desired compound N,N-dimethyl-2- 2-(2,5-dimethylphenoxy-methyl)phenyl!butylamide (0.06 g, 29%) as white crystals and 2- 2-(2,5-dimethylphenoxymethyl)phenyl!-N-methylbutylamide (0.11 g, 55%) as white crystals.

Compound No. 163; mp.: 62-62.5° C.

NMR (δ ppm, TMS/CDCl₃): 0.94(3H,t,J=7.3), 1.62-1.77(1H,m), 2.09-2.26(1H,m), 2.14(3H,s), 2.36(3H,s), 2.85 (3H,s), 2.95(3H,s), 3.93(1H,dd,J=9.1,4.9), 4.96(1H,d,J=11.0), 5.15(1H,d,J=11.0), 6.73(1H,d,J=7.3), 6.80(1H,s), 7.05 (1H,d,J=7.9), 7.23-7.46(4H,m).

Compound No. 146; mp.: 108-110° C.

NMR (δ ppm TMS/CDCl₃): 0.86(3H,t,J=7.3), 1.77-1.88(1H,m), 2.16(3H,s), 2.16-2.29(1H,m), 2.35(3H,s), 2.67 (3H,d,J=4.9), 3.63(1H,t,J=7.3), 4.84(1H,d,J=11.0), 5.24 (1H,d,J=11.0), 5.80(1H,brs), 6.76(1H,d,J=7.3), 6.84(1H,s), 7.06(1H,d,J=7.3), 7.27(1H,t,J=7.3), 7.38(2H;t,J=7.3), 7.49 (1H,d,J=7.3).

Example 15 Synthesis of methyl 2- 2-(2,5-dimethylphenoxy-methyl)phenyl!butyrate (Compound No. 145)

A solution of 2- 2-(2,5-dimethylphenoxymethyl)-phenyl!butyronitrile (0.67 g, 2.4 mmol) and 96% sodium hydroxide (0.73 g, 17.5 mmol) in ethanol (8 ml) was heated under reflux for 43 hours. The solvent was evaporated, and then water was added. The mixture was adjusted to pH 3 with 1N hydrochloric acid and extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and then the solvent was evaporated. The crude product was dissolved in N,N-dimethylformamide (5 ml) and stirred at room temperature. Methyl iodide (0.50 g, 3.5 mmol) and potassium carbonate (0.50 g, 3.6 mmol) were added thereto in this order. After 1 hour, water was added, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=9/1) to give the desired compound methyl 2- 2-(2,5-dimethylphenoxymethyl)phenyl!butyrate (0.62 g, 83%) as white crystals.

mp.: 62-65° C.

NMR (δ ppm, TMS/CDCl₃): 0.91(3H,t,J=7.3), 1.78-1.89 (1H,m), 2.07-2.21(1H,m), 2.18(3H,s), 2.34(3H,s), 3.64(3H,s), 3.84(1H,t,J=7.3), 5.02(1H,d,J=11.0), 5.19 (1H,d,J=11.0), 6.71 (1H,d,J=7.3), 6.78(1H,s), 7.04(1H,d,J=7.3), 7.27-7.44(2H,m), 7.44-7.47(2H,m).

Example 16 Synthesis of α-methoxy-N-methyl-(2,3,5-trimethyl-phenoxymethyl)phenylacetamide (Compound No. 465)

A solution of 2-chloromethyl-α-methoxy-N-methyl-phenylacetamide (0.25 g, 1.1 mmol) and 2,3,5-trimethylphenol (0.18 g, 1.3 mmol) in N,N-dimethylformamide (3 ml) was stirred at 0° C., and 60% oily sodium hydride (0.08 g, 2.0 mmol) was added thereto. The mixture was stirred at 0° C. for 70 minutes and then at room temperature for 1 hour, and ice and water were added in this order. The mixture was extracted with ethyl acetate, washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=7/3) to give the desired compound α-methoxy-N-methyl-(2,3,5-trimethylphenoxymethyl)phenylacetamide (0.17 g, 50%) as an oil.

NMR (δ ppm, TMS/CDCl₃): 2.11(3H,s), 2.23(3H,s), 2.29(3H,s), 2.81(3H,d,J=4.9), 3.35(3H,s), 5.03(1H,s), 5.03(1H,d,J=11.6), 5.44(1H,d,J=11.6), 6.64(1H,s), 6.68(1H,s), 6.80(1H,brs), 7.32-7.43(3H,m), 7.50-7.53(1H,m).

Example 17 Synthesis of (3-chloro-5-trifluoromethyl-2-pyridyloxymethyl)-α-methoxy-N-methyl-phenylacetamide (Compound No. 427)

A solution of 2-hydroxymethyl-α-methoxy-N-methyl-phenylacetamide (1.00 g, 4.8 mmol) in N,N-dimethylformamide (5 ml) was stirred at 0° C., and 60% oily sodium hydride (0.19 g, 4.8 mmol) was added thereto. The mixture was stirred at 0° C. for 30 minutes, and then 2,3-dichloro-5-trifluoromethyl-pyridine (1.24 g, 5.7 mmol) was added. The mixture was stirred at 0° C. for 2 hours, and then ice and water were added in this order. The mixture was extracted with ether, washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=1/1) to give the desired compound (3-chloro-5-trifluoro-methyl-2-pyridyloxymethyl)-α-methoxy-N-methyl-phenylacetamide (1.40 g, 75%) as white crystals.

mp.: 133-135° C.

NMR (δ ppm, TMS/CDCl₃): 2.83(3H,d,J=4.9), 3.38 (3H,s), 5.19(1H,s), 5.60(1H,d,J=12.2), 5.92(1H,d,J=12.2), 6.80 (1H,brs), 7.28-7.40(3H,m), 7.55-7.58(1H,m), 7.84(1H,s), 8.32 (1H,s).

Example 18

According to the same manner as that described in Examples 4 to 17, various compounds of the formula (I) were synthesized. The compounds thus obtained and the physical data of their representative compounds are shown below. In the tables, U, V and W mean the substituents in the group of the formula (XX) represented by Q. In the tables, the compounds obtained in Examples 4 to 17 and their physical data are also listed.

    __________________________________________________________________________     Comp.                                                                          No. X   R.sup.1 Z Y    M    n U        V    W                                  __________________________________________________________________________     139 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  140 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  141 H   OCH.sub.2 OCH.sub.3                                                                    O OCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  142 H   OCH.sub.2 OCH.sub.3                                                                    O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  143 H   OCOCH.sub.3                                                                            O OCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  144 H   OCOCH.sub.3                                                                            O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  145 H   C.sub.2 H.sub.5                                                                        O OCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  146 H   C.sub.2 H.sub.5                                                                        O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  147 H   NH.sub.2                                                                               O OCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  148 H   NH.sub.2                                                                               O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  149 H   Cl      O OCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  150 H   Cl      O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  151 H   OC.sub.2 H.sub.5                                                                       O OCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  152 H   OC.sub.4 H.sub.9                                                                       O OCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  153 H   OCH.sub.2 CH═CH.sub.2                                                              O OCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  154 H   CF.sub.3                                                                               O OCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  155 H   CC.sub.2 H.sub.5                                                                       O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  156 H   OC.sub.4 H.sub.9                                                                       O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  159 H   C.sub.2 H.sub.5                                                                        O NH.sub.2                                                                            O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  160 H   SCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  161 H   OCH.sub.3                                                                              O NH.sub.2                                                                            O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  162 H   SCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  163 H   C.sub.2 H.sub.5                                                                        O N(CH.sub.3).sub.2                                                                   O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  165 H   OCH.sub.3                                                                              O N(CH.sub.3).sub.2                                                                   O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  166 H   OC.sub.2 H.sub.5                                                                         N(CH.sub.3).sub.2                                                                   O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  167 H   C.sub.2 H.sub.5                                                                        O OH   O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  169 H   OCH.sub.3                                                                              S OCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  170 H   OCH.sub.3                                                                              S NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  171 H   OCOCH.sub.3                                                                            O NHCH.sub.3                                                                          O    0 H        H    H                                  173 H   OCOCH.sub.3                                                                            O NHCH.sub.3                                                                          O    0 2-CH.sub.3                                                                              H    H                                  174 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 4-Cl     H    H                                  175 H   C.sub.2 H.sub.5                                                                        O OH   O    0 4-OCH.sub.3                                                                             H    H                                  176 H   OCH.sub.3                                                                              O SCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  177 H   C.sub.2 H.sub.5                                                                        O NH.sub.2                                                                            O    0 4-OCH.sub.3                                                                             H    H                                  178 H   OCOCH.sub.3                                                                            O NHCH.sub.3                                                                          O    0 3-CH.sub.3                                                                              4-CH.sub.3                                                                          H                                  179 H   OCH.sub.3                                                                              O N(CH.sub.3).sub.2                                                                   O    1 2-CH.sub.3                                                                              H    H                                  180 H   C.sub.2 H.sub.5                                                                        O OCH.sub.3                                                                           O    0 4-OCH.sub.3                                                                             H    H                                  181 H   OCOCH.sub.3                                                                            O OCH.sub.3                                                                           O    0 H        H    H                                  182 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    0 H        H    H                                  183 H   OC.sub.2 H.sub.5                                                                       O OCH.sub.3                                                                           O    0 H        H    H                                  184 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 H        H    H                                  185 H   OCH.sub.3                                                                              O OC.sub.2 H.sub.5                                                                    O    1 2-CH.sub.3                                                                              4-Cl H                                  186 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              4-Cl H                                  188 H   OC.sub.2 H.sub.5                                                                       O NHCH.sub.3                                                                          O    0 H        H    H                                  189 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 4-Cl     H    H                                  193 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 2-Cl     H    H                                  194 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              H    H                                  195 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 H        H    H                                  196 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-Cl     H    H                                  197 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              H    H                                  198 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 H        H    H                                  205 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 3-Cl     5-Cl H                                  206 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 2-Cl     4-Cl H                                  207 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 3-CF.sub.3                                                                              H    H                                  208 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 4-OCH.sub.3                                                                             H    H                                  209 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 4-CH.sub.3                                                                              H    H                                  210 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 3-CH.sub.3                                                                              H    H                                  211 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 4-CH.sub.3                                                                              H    H                                  212 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 3-CH.sub.3                                                                              H    H                                  213 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 3-Cl     5-Cl H                                  214 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 3-CF.sub.3                                                                              H    H                                  215 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 4-OCH.sub.3                                                                             H    H                                  216 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              3-CH.sub.3                                                                          H                                  217 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              3-CH.sub.3                                                                          H                                  218 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              4-CH.sub.3                                                                          H                                  219 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              4-CH.sub.3                                                                          H                                  220 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 3-CH.sub.3                                                                              4-CH.sub.3                                                                          H                                  221 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 3-CH.sub.3                                                                              4-CH.sub.3                                                                          H                                  222 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 3-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  223 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 3-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  224 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              3-CH.sub.3                                                                          4-CH.sub.3                         225 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              3-CH.sub.3                                                                          4-CH.sub.3                         226 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              4-CH.sub.3                                                                          5-CH.sub.3                         227 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              4-CH.sub.3                                                                          5-CH.sub.3                         228 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 3-CH.sub.3                                                                              4-CH.sub.3                                                                          5-CH.sub.3                         229 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 3-CH.sub.3                                                                              4-CH.sub.3                                                                          5-CH.sub.3                         230 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 3-Cl     H    H                                  231 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 3-Cl     H    H                                  232 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 2-Br     H    H                                  233 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-Br     H    H                                  234 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 4-Br     H    H                                  235 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 4-Br     H    H                                  236 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 4-F      H    H                                  237 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 4-F      H    H                                  238 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 4-I      H    H                                  239 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 4-I      H    H                                  240 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 3-Cl     4-Cl H                                  241 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 3-Cl     4-Cl H                                  242 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 2-Cl     5-Cl H                                  243 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-Cl     5-Cl H                                  244 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 2-OCH.sub.3                                                                             H    H                                  245 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-OCH.sub.3                                                                             H    H                                  246 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 3-OCH.sub.3                                                                             H    H                                  247 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 3-OCH.sub.3                                                                             H    H                                  248 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 3-OC.sub.2 H.sub.5                                                                      H    H                                  249 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 3-OC.sub.2 H.sub.5                                                                      H    H                                  250 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 3-OCH.sub.2 CH═CH.sub.2                                                             H    H                                  251 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 3-OCH.sub.2 CH═CH.sub.2                                                             H    H                                  252 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 4-OCH.sub.2 C.tbd.CH                                                                    H    H                                  253 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 4-OCH.sub.2 C.tbd.CH                                                                    H    H                                  254 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 2-OCHF.sub.2                                                                            H    H                                  255 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-OCHF.sub.2                                                                            H    H                                  256 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 4-OCHF.sub.2                                                                            H    H                                  257 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 4-OCHF.sub.2                                                                            H    H                                  258 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 3-OPh    H    H                                  259 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 3-OPh    H    H                                  260 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 3-OCH.sub.3                                                                             4-OCH.sub.3                                                                         H                                  261 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 3-OCH.sub.3                                                                             4-OCH.sub.3                                                                         H                                  262 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-Cl     4-Cl H                                  263 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              4-Cl H                                  264 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              4-Br H                                  265 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              4-Br H                                  266 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 2-Cl     4-CH.sub.3                                                                          H                                  267 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-Cl     4-CH.sub.3                                                                          H                                  268 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 3-CH.sub.3                                                                              4-Cl H                                  269 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 3-CH.sub.3                                                                              4-Cl H                                  270 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              3-CH.sub.3                                                                          4-Cl                               271 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              3-CH.sub.3                                                                          4-Cl                               272 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 3-Cl     4-CH.sub.3                                                                          5-Cl                               273 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-Cl     5-CF.sub.3                                                                          H                                  274 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-Cl     4-OCH.sub.3                                                                         H                                  275 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-Br     4-OCH.sub.3                                                                         H                                  276 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 3-Cl     4-OCH.sub.3                                                                         H                                  277 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 3-OCH.sub.3                                                                             4-Cl H                                  278 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 3-Cl     4-OCH.sub.3                                                                         5-Cl                               279 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-Cl     4-OCHF.sub.2                                                                        H                                  280 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 3-Cl     4-OCHF.sub.2                                                                        H                                  281 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              4-OCH.sub.3                                                                         H                                  282 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-OCH.sub.3                                                                             4-CH.sub.3                                                                          H                                  283 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              4-OCHF.sub.2                                                                        H                                  285 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    0 4-Cl     H    H                                  286 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 4-Cl     H    H                                  288 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    0 4-CH.sub.3                                                                              H    H                                  289 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 4-CH.sub.3                                                                              H    H                                  291 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    0 3-CH.sub.3                                                                              4-CH.sub.3                                                                          H                                  292 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-CH.sub.3                                                                              4-CH.sub.3                                                                          H                                  293 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 2-CH.sub.3                                                                              H    H                                  294 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    0 3-CH.sub.3                                                                              H    H                                  295 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-CH.sub.3                                                                              H    H                                  296 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    0 3-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  297 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  298 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-CH.sub.3                                                                              4-CH.sub.3                                                                          5-CH.sub.3                         299 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 4-C.sub.2 H.sub.5                                                                       H    H                                  300 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    0 3-CF.sub.3                                                                              H    H                                  301 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-CF.sub.3                                                                              H    H                                  302 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    0 3-Cl     H    H                                  303 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-Cl     H    H                                  304 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    0 3-Br     H    H                                  305 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-Br     H    H                                  306 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    0 4-Br     H    H                                  307 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 4-Br     H    H                                  308 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    0 4-F      H    H                                  309 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 4-F      H    H                                  310 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 4-I      H    H                                  311 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-Cl     4-Cl H                                  312 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 2-Cl     H    H                                  313 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-OCH.sub.3                                                                             H    H                                  314 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-OC.sub.3 H.sub.7                                                                      H    H                                  315 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    0 4-OCH.sub.3                                                                             H    H                                  316 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 4-OCH.sub.3                                                                             H    H                                  317 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 4-OC.sub.2 H.sub.5                                                                      H    H                                  318 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-OCH.sub.3                                                                             4-OCH.sub.3                                                                         H                                  319 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-OCHF.sub.2                                                                            H    H                                  320 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 4-OCHF.sub.2                                                                            H    H                                  321 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-OCH.sub.2 CH═CH.sub.2                                                             H    H                                  322 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 4-OCH.sub.2 CH═CH.sub.2                                                             H    H                                  323 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-OCH.sub.2 C.tbd.CH                                                                    H    H                                  324 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-OCH.sub.2 C.tbd.CCH.sub.3                                                             H    H                                  325 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 4-OCH.sub.2 C.tbd.CH                                                                    H    H                                  326 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-OPh    H    H                                  327 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 4-OPh    H    H                                  328 H   OCH.sub.3                                                                              O OCH.sub.3                                                                           O    0 3-CH.sub.3                                                                              4-Cl H                                  329 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-CH.sub.3                                                                              4-Cl H                                  330 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-Cl     4-CH.sub.3                                                                          H                                  331 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 2-Cl     5-CF.sub.3                                                                          H                                  332 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-CH.sub.3                                                                              4-OCH.sub.3                                                                         H                                  333 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-OCH.sub.3                                                                             4-CH.sub.3                                                                          H                                  334 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-CH.sub.3                                                                              4-OCHF.sub.2                                                                        H                                  335 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-OCHF.sub.2                                                                            4-CH.sub.3                                                                          H                                  336 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-OCH.sub.3                                                                             4-Cl H                                  337 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-Cl     4-OCH.sub.3                                                                         H                                  338 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-OCHF.sub.2                                                                            4-Cl H                                  339 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-Cl     4-OCHF.sub.2                                                                        H                                  340 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 2-Cl     4-CH.sub.3                                                                          5-OCH.sub.3                        341 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-CH.sub.2 CH                                                                           4-CH.sub.3                                                                          H                                                                ═CH.sub.2                                    342 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-CH.sub.3                                                                              4-OCH.sub.2 C                                                                       H                                                                         .tbd.CH                                 343 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-CH.sub.2 CH                                                                           4-Cl H                                                                ═CH.sub.2                                    344 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 3-Cl     4-OCH.sub.2 C                                                                       H                                                                         .tbd.CH                                 345 4-Cl                                                                               OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  346 5-Cl                                                                               OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  347 4-CH.sub.3                                                                         OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  348 5-CH.sub.3                                                                         OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  349 4-OCH.sub.3                                                                        OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  350 5-OCH.sub.3                                                                        OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  351 H   OCH.sub.2 C                                                                            O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                          .tbd.CH                                                                352 H   OCHF.sub.2                                                                             O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  353 H   OCOSCH.sub.3                                                                           O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  354 H   OSO.sub.2 CH.sub.3                                                                     O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  355 H   OSO.sub.2 Ph--                                                                         O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                          4-CH.sub.3                                                             356 H   OCONHCH.sub.3                                                                          O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  357 H   OCON(CH.sub.3).sub.2                                                                   O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  358 H   SOCH.sub.3                                                                             O OCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  359 H   SO.sub.2 CH.sub.3                                                                      O OCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  360 H   SOCH.sub.3                                                                             O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  361 H   SO.sub.2 CH.sub.3                                                                      O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  362 H   NHCH.sub.3                                                                             O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  363 H   N(CH.sub.3).sub.2                                                                      O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  364 H   NO.sub.2                                                                               O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  365 H   NO.sub.2                                                                               O NHCH.sub.3                                                                          O    0 H        H    H                                  366 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          S    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  367 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          NH   1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  368 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          NCH.sub.3                                                                           1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  369 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          NCHO 1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  370 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          NCOCH.sub.3                                                                         1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  371 H   OCH.sub.3                                                                              S NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              H    H                                  372 H   OCH.sub.3                                                                              S NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              4-Cl H                                  373 H   SCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              H    H                                  374 H   SCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              4-Cl H                                  375 H   OC.sub.2 H.sub.5                                                                       O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              H    H                                  376 H   OC.sub.2 H.sub.5                                                                       O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              4-Cl H                                  377 H   SCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 H        H    H                                  379 H   SCH.sub.3                                                                              O NHCH.sub.3                                                                          O    0 4-CH.sub.3                                                                              H    H                                  380 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 4-SCH.sub.3                                                                             H    H                                  381 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          S    1 2-CH.sub.3                                                                              H    H                                  382 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          S    1 2-CH.sub.3                                                                              4-Cl H                                  383 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 4-SCH.sub.3                                                                             H    H                                  384 H   CH.sub.3                                                                               O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  385 H   OCOC.sub.2 H.sub.5                                                                     O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  386 H   OCH.sub.3                                                                              O NHC.sub.2 H.sub.5                                                                   O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  387 H   OCH.sub.3                                                                              O NH.sub.2                                                                            O    1 2-CH.sub.3                                                                              H    H                                  388 H   OCH.sub.3                                                                              O NH.sub.2                                                                            O    1 2-CH.sub.3                                                                              4-Cl H                                  __________________________________________________________________________     Comp.                                                                          No.   X  R.sup.1                                                                              Z  Y     M  n   Q                                               __________________________________________________________________________     389   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  0   6-Cl-pyrimidin-4-yl                             390   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  0   4,6-(CH.sub.3).sub.2 -pyrimidin-4-yl            391   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  0   3,5-Cl.sub.2 -pyridin-2-yl                      392   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  0   5-Cl-pyridin-2-yl                               393   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  0   5-CF.sub.3 -pyridin-2-yl                        394   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  0   5-CF.sub.3 -6-Cl-pyridin-2-yl                   395   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  0   Quinolin-4-yl                                   396   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  0   Quinazolin-4-yl                                 397   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  0   Benzothiazol-2-yl                               398   H  OCH.sub.3                                                                            O  OCH.sub.3                                                                            O  1   Benzothiazol-2-yl                               399   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  1   Benzothiazol-2-yl                               400   H  OCH.sub.3                                                                            O  OCH.sub.3                                                                            O  1   Quinolin-4-yl                                   401   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  1   Quinolin-4-yl                                   402   H  OCH.sub.3                                                                            O  OCH.sub.3                                                                            O  1   Quinazolin-4-yl                                 403   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  1   Quinazolin-4-yl                                 404   H  OCH.sub.3                                                                            O  OCH.sub.3                                                                            O  1   1,3-(CH.sub.3).sub.2 -4-CO.sub.2 CH.sub.3                                      -pyrazol-5-yl                                   405   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  1   1,3-(CH.sub.3).sub.2 -4-CO.sub.2 CH.sub.3                                      -pyrazol-5-yl                                   406   H  OCH.sub.3                                                                            O  OCH.sub.3                                                                            O  1   1-CH.sub.3 -4-CHO-pyrazol-5-yl                  407   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  1   1-CH.sub.3 -4-CHO-pyrazol-5-yl                  408   H  OCH.sub.3                                                                            O  OCH.sub.3                                                                            O  1   5-CO.sub.2 C.sub.2 H.sub.5 -6-C.sub.2                                          H.sub.5 -pyrimidin-4-yl                         409   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  1   5-CO.sub.2 C.sub.2 H.sub.5 -6-C.sub.2                                          H.sub.5 -pyrimidin-4-yl                         410   H  OCH.sub.3                                                                            O  OCH.sub.3                                                                            O  1   4,6-(CH.sub.3).sub.2 -pyrimidin-2-yl            411   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  1   4,6-(CH.sub.3).sub.2 -pyrimidin-2-yl            412   H  OCH.sub.3                                                                            O  OCH.sub.3                                                                            O  1   6-Cl-pyrimidin-4-yl                             413   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  1   6-Cl-pyrimidin-4-yl                             414   H  OCH.sub.3                                                                            O  OCH.sub.3                                                                            O  1   5-Cl-6-CH.sub.3 -pyrimidin-4-yl                 415   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  1   5-Cl-6-CH.sub.3 -pyrimidin-4-yl                 416   H  OCH.sub.3                                                                            O  OCH.sub.3                                                                            O  1   5-CF.sub.3 -6-Cl-pyridin-2-yl                   417   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  1   5-CF.sub.3 -6-Cl-pyridin-2-yl                   418   H  OH    O  NHCH.sub.3                                                                           O  1   3-CF.sub.3 -6-Cl-pyridin-2-yl                   419   H  OCH.sub.3                                                                            O  OCH.sub.3                                                                            O  1   3-CF.sub.3 -6-Cl-pyridin-2-yl                   420   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  1   3-CF.sub.3 -6-Cl-pyridin-2-yl                   421   H  OH    O  NHCH.sub.3                                                                           O  1   3-CF.sub.3 -pyridin-2-yl                        422   H  OCH.sub.3                                                                            O  OCH.sub.3                                                                            O  1   3-CF.sub.3 -pyridin-2-yl                        423   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  1   3-CF.sub.3 -pyridin-2-yl                        425   H  OH    O  NHCH.sub.3                                                                           O  1   3-Cl-5-CF.sub.3 -pyridin-2-yl                   426   H  OCH.sub.3                                                                            O  OCH.sub.3                                                                            O  1   3-Cl-5-CF.sub.3 -pyridin-2-yl                   427   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  1   3-Cl-5-CF.sub.3 -pyridin-2-yl                   428   H  OH    O  NHCH.sub.3                                                                           O  1   5-CF.sub.3 -pyridin-2-yl                        429   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  1   5-CF.sub.3 -pyridin-2-yl                        430   H  OCH.sub.3                                                                            O  OCH.sub.3                                                                            O  1   5-CF.sub.3 -pyridin-2-yl                        431   H  OH    O  NHCH.sub.3                                                                           O  1   3,5-Cl.sub.2 -pyridin-2-yl                      432   H  OCH.sub.3                                                                            O  OCH.sub.3                                                                            O  1   3,5-Cl.sub.2 -pyridin-2-yl                      433   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  1   3,5-Cl.sub.2 -pyridin-2-yl                      434   H  OH    O  NHCH.sub.3                                                                           O  1   2-Cl-pyridin-3-yl                               436   H  OCH.sub.3                                                                            O  OCH.sub.3                                                                            O  1   2-Cl-pyridin-3-yl                               437   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  1   2-Cl-pyridin-3-yl                               __________________________________________________________________________     Comp.                                                                          No.   X  R.sup.1                                                                              Z  Y     M  n   U      V     W                                  __________________________________________________________________________     438   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  1   4-CH.sub.2 OCH.sub.3                                                                  H     H                                  439   H  NO.sub.2                                                                             O  OCH.sub.3                                                                            O  1   2-CH.sub.3                                                                            5-CH.sub.3                                                                           H                                  __________________________________________________________________________     Comp.                                                                          No.   X  R.sup.1                                                                              Z  Y     M  n   Q                                               __________________________________________________________________________     441   H  OH    O  NHCH.sub.3                                                                           O  1   5-CF.sub.3 -6-Cl-pyridin-2-yl                   443   O  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  1   5-Cl-pyridin-2-yl                               446   H  OH    O  NHCH.sub.3                                                                           O  1   3-CF.sub.3 -5-Cl-pyridin-2-yl                   447   H  OCH.sub.3                                                                            O  OCH.sub.3                                                                            O  1   3-CF.sub.3 -5-Cl-pyridin-2-yl                   448   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  1   3-CF.sub.3 -5-Cl-pyridin-2-yl                   451   H  OH    O  NHCH.sub.3                                                                           O  1   6-CF.sub.3 -pyridin-2-yl                        __________________________________________________________________________     Comp.                                                                          No.   X  R.sup.1                                                                              Z  Y     M  n   Q                                               __________________________________________________________________________     452   H  OCH.sub.3                                                                            O  OCH.sub.3                                                                            O  1   6-CF.sub.3 -pyridin-2-yl                        453   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  1   6-CF.sub.3 -pyridin-2-yl                        454   H  OCH.sub.3                                                                            O  OCH.sub.3                                                                            O  1   5-Cl-pyridin-2-yl                               455   H  OH    O  NHCH.sub.3                                                                           O  1   5-Cl-pyridin-2-yl                               457   H  OH    O  NHCH.sub.3                                                                           O  1   5-CF.sub.3 -3,6-Cl.sub.2 -pyridin-2-yl          458   H  OCH.sub.3                                                                            O  OCH.sub.3                                                                            O  1   5-CF.sub.3 -3,6-Cl.sub.2 -pyridin-2-yl          459   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  1   5-CF.sub.3 -3,6-Cl.sub.2 -pyridin-2-yl          __________________________________________________________________________     Comp.                                                                          No. X   R.sup.1 Z Y    M    n U        V    W                                  __________________________________________________________________________     460 H   OCH.sub.3                                                                              S NH.sub.2                                                                            O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  461 H   OC.sub.4 H.sub.9                                                                       S NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  462 H   NH.sub.2.HCl                                                                           O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  463 H   NH.sub.2.HCl                                                                           O OCH.sub.3                                                                           O    1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  465 H   OCH.sub.3                                                                              O NHCH.sub.3                                                                          O    1 2-CH.sub.3                                                                              3-CH.sub.3                                                                          5-CH.sub.3                         __________________________________________________________________________     Comp.                                                                          No.   X  R.sup.1                                                                              Z  Y     M  n   Q                                               __________________________________________________________________________     466   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  1   3-Cl-pyridin-2-yl                               467   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           O  1   3-CH.sub.3 -pyridin-2-yl                        468   H  OCH.sub.3                                                                            O  NHCH.sub.3                                                                           S  1   3,5-Cl.sub.2 -pyridin-2-yl                      __________________________________________________________________________     Comp.                                                                          No. X   R.sup.1                                                                             Z    Y      M  n U        V    W                                  __________________________________________________________________________     469 H   OCH.sub.3                                                                           O    N(CH.sub.3)C.sub.2 H.sub.5                                                            O  1 2-CH.sub.3                                                                              4-Cl H                                  470 H   OCH.sub.3                                                                           O    OH     O  1 2-CH.sub.3                                                                              5-CH.sub.3                                                                          H                                  471 H   OCH.sub.3                                                                           S    N(CH.sub.3).sub.2                                                                     O  1 2-CH.sub.3                                                                              H    H                                  472 H   OCH.sub.3                                                                           O    NCH.sub.3                                                                             O  1 2-Cl     5-CH.sub.3                                                                          H                                  473 H   OCH.sub.3                                                                           O    NCH.sub.3                                                                             O  1 2-CH.sub.3                                                                              6-CH.sub.3                                                                          H                                  __________________________________________________________________________     Comp.                                                                          No.        mp or .sup.1 H-NMR(CDCl.sub.3) δ ppm                          __________________________________________________________________________     139        2.21(3H, s), 2.33(3H, s), 3.40(3H, s), 3.70(3H, s), 5.10(1H,                   d,                                                                             J=12.2), 5.14(1H, s), 5.28(1H, d, J=12.2), 6.71(1H, d,                         J=7.3),                                                                        6.76(1H, s), 7.04(1H, d, J=7.3), 7.33-7.40(2H, m), 7.50-7.56                   (2H, m)                                                             140        86-88° C.                                                    141        2.23(3H, s), 2.32(3H, s), 3.36(3H, s), 3.71(3H, s), 4.67(1H,                   d,                                                                             J=6.7), 4.75(1H, d, J=6.7), 5.17(1H, d, J=12.2), 5.23(1H, d,                   J=12.2), 5.49(1H, s), 6.71(1H, d, J=7.9), 6.75(1H, s),                         7.04(1H, d,                                                                    J=7.3), 7.34-7.40(2H, m), 7.53-7.57(2H, m)                          142        81-82° C.                                                    143        77-80° C.                                                    144        114-115° C.                                                  145        62-65° C.                                                    146        108-110° C.                                                  149        2.20(3H, s), 2.35(3H, s), 3.76(3H, s), 5.14(2H, s), 5.84(1H,                   s),                                                                            6.73(1H, d, J=7.3), 6.77(1H, s), 7.05(1H, d, J=7.3), 7.38-                     7.48(3H, m), 7.66(1H, d, J=7.3)                                     150        111˜113° C.                                            151        1.26(3H, t, J=7.3), 2.21(3H, s), 2.32(3H, s), 3.42-3.67(2H,                    m),                                                                            3.70(3H, s), 5.12(1H, d, J=12.2), 5.23(1H, s), 5.28(1H, d,                     J=12.2),                                                                       6.70(1H, d, J=7.3), 6.75(1H, s), 7.04(1H, d, J=7.3), 7.32-                     7.38(2H, m), 7.49-7.58(2H, m)                                       152        0.89(3H, t, J=7.3), 1.32-1.45(2H, m), 1.57-1.68(2H, m),                        2.22(3H,                                                                       s), 2.33(3H, s), 3.39-3.47(1H, m), 3.52-3.60(1H, m), 3.70(3H,                  s),                                                                            5.12(1H, d, J=12.2), 5.20(1H, s), 5.27(1H, d, J=12.2),                         6.71(1H, d,                                                                    J=7.9), 6.75(1H, s), 7.04(1H, d, J=7.3), 7.34-7.39(2H, m),                     7.52-                                                                          7.55(2H, m)                                                         155        98-100° C.                                                   156        58-60° C.                                                    159        100-101° C.                                                  161        2.19(3H, s), 2.32(3H, s), 3.36(3H, s), 5.02(1H, s), 5.07(1H,                   d,                                                                             J=11.6), 5.40(1H, d, J=11.6), 5.88(1H, brs), 6.70(1H, d,                       J=7.3),                                                                        6.71(1H, brs), 6.78(1H, s), 7.03(1H, d, J=7.3), 7.32-7.40(2H,                  m),                                                                            7.42-7.48(1H, m), 7.50-7.53(1H, m)                                  162        2.10(3H, s), 2.20(3H, s), 2.34(3H, s), 3.71(3H, s), 4.95(1H,                   s),                                                                            5.13(2H, s), 6.72(1H, d, J=7.3), 6.77(1H, s), 7.04(1H, d,                      J=7.3),                                                                        7.30-7.40(2H, m), 7.46(1H, dd, J=7.3, 1.8), 7.68(1H, dd,                       J=7.3,                                                                         1.8)                                                                163        62-62.5° C.                                                  165        2.17(3H, s), 2.33(3H, s), 2.87(3H, s), 3.00(3H, s), 3.44(3H,                   s),                                                                            5.02(1H, d, J=11.6), 5.26(1H, d, J=11.6), 5.32(1H, s),                         6.71(1H, d,                                                                    J=7.3), 6.79(1H, s), 7.03(1H, d, J=7.3), 7.30-7.40(3H, m),                     7.50-                                                                          7.54(1H, m)                                                         166        80-81° C.                                                    170        2.20(3H, s), 2.32(3H, s), 3.23(3H, d, J=4.8), 3.35(3H, s),                     5.12(1H,                                                                       d, J=11.6), 5.40(1H, s), 5.58(1H, d, J=11.6), 6.70(1H, d,                      J=7.3),                                                                        6.81(1H, s), 7.03(1H, d, J=7.3), 7.28-7.38(3H, m),                             7.48-7.52(1H,                                                                  m), 8.78(1H, brs)                                                   171        2.10(3H, s), 2.78(3H, d, J=4.8), 6.18(1H, brs), 6.34(1H, s),                   6.87(1H, dd, J=8.2, 1.0), 6.97-7.00(2H, m), 7.11-7.16(2H, m),                  7.26-7.36(3H, m), 7.58(1H, dd, J=7.8, 1.7)                          173        2.15(3H, s), 2.25(3H, s), 2.74(3H, d, J=4.9), 5.10(1H, d,                      J=11.9),                                                                       5.44(1H, d, J=11.9), 6.29(1H, brs), 6.36(1H, s), 6.91(1H, t,                   J=7.3),                                                                        6.98(1H, d, J=7.3), 7.14-7.19(2H, m), 7.34-7.40(2H, m), 7.46-                  7.56(2H, m)                                                         174        3.39(3H, s), 3.70(3H, s), 5.05(1H, s), 5.09(1H, d, J=12.0),                    5.25(1H, d, J=12.0), 6.86-6.92(2H, m), 7.22-7.26(2H, m),                       7.35-                                                                          7.38(2H, m), 7.45-7.49(2H, m)                                       175        1.11(3H, t, J=7.3), 1.99(2H, quintet, J=7.3), 3.81(3H, s),                     4.24(1H,                                                                       t, J=7.3), 6.74(1H, dd; J=7.9, 1.2), 6.87-6.97(4H, m),                         7.11(1H,                                                                       ddd, J=7.9, 7.6, 1.2), 7.21(1H, ddd, J=7.9, 7.6, 1.8),                         7.49(1H, dd,                                                                   J=7.6, 1.8)                                                         176        2.20(3H, s), 2.23(3H, s), 2.32(3H, s), 3.46(3H, s), 5.05(1H,                   d, J=                                                                          12.2), 5.15(1H, s), 5.34(1H, d, J=12.2), 6.70(1H, d, J=7.3),                   6.76(1H, s), 7.03(1H, d, J=7.3), 7.32-7.40(2H, m),                             7.47-7.57(2H,                                                                  m)                                                                  177        65-67° C.                                                    178        2.12(3H, s), 2.23(6H, s), 2.78(3H, d, J=4.9), 6.26(1H, brs),                   6.36(1H, s), 6.72(1H, dd, J=7.9, 1.8), 6.80(1H, s), 6.82(1H,                   d,                                                                             J=7.9), 7.09(2H, t, J=7.3), 7.25(1H, dt, J=1.8, 7.9), 7.56(1H,                 dd,                                                                            J=7.3, 1.8)                                                         179        98-99.5° C.                                                  180        0.91(3H, t, J=7.3), 1.65-1.92(1H, m), 2.04-2.17(1H, m),                        3.61(3H,                                                                       s), 3.78(3H, s), 3.98(1H, t, J=7.3), 6.78(1H, dd, J=7.9, 1.8),                 6.82-                                                                          6.93(4H, m), 7.05(1H, t, J=7.3), 7.15(1H, dt, J=7.9, 1.8),                     7.35(1H,                                                                       dd, J=7.3, 1.8)                                                     181        39-41° C.                                                    182        3.41(3H, s), 3.66(3H, s), 5.24(1H, s), 6.90(1H, d, J=7.9),                     6.99(2H,                                                                       d, J=7.3), 7.10(1H, t, J=7.3), 7.25-7.36(3H, m), 7.52(1H, dd,                  J=7.9, 1.8)                                                         183        1.21(3H, t, J=7.3), 3.44-3.65(2H, m), 3.64(3H, s), 5.35(1H,                    s),                                                                            6.88(1H, t, J=7.9), 6.98(2H, d, J=7.9), 7.08(1H, t, J=7.3),                    7.14(1H,                                                                       t, J=7.3), 7.23-7.34(3H, m), 7.55(1H, dd, J=7.9, 1.8)               184        2.82(3H, d, J=4.9), 3.35(3H, s), 5.03(1H, s), 6.82(1H, brs),                   6.88(1H, d, J=7.9), 7.04(2H, d, J=7.9), 7.12(2H, t, J=7.9),                    7.23-                                                                          7.42(4H, m)                                                         185        1.20(3H, d, J=7.3), 2.24(3H, s), 3.40(3H, s), 4.08-4.27(2H,                    m),                                                                            5.06(1H, s), 5.14(1H, d, J=12.2), 5.29(1H, d, J=12.2),                         6.83(1H, d,                                                                    J=7.9), 7.08-7.13(2H, m), 7.33-7.39(2H, m), 7.47-7.55(2H, m)        186        111-113° C.                                                  188        1.16(3H, t, J=7.3), 2.82(3H, d, J=4.9), 3.50(2H, q, J=7.3),                    5.15(1H, s), 6.86(1H, d, J=7.9), 6.90(1H, brs), 7.03(2H, d,                    J=7.9),                                                                        7.09(2H, t, J=7.9), 7.20-7.37(4H, m)                                189        87-88° C.                                                    193        3.42(3H, s), 3.70(3H, s), 5.15(1H, s), 5.20(1H, d, J=12.0),                    5.39(1H, d, J=12.0), 6.93(1H, dt, J=1.8, 8.0), 7.03(1H, d,                     J=8.0),                                                                        7.21(1H, dt, J=1.8, 8.0), 7.36-7.40(3H, m), 7.51-7.59(2H, m)        194        2.26(3H, s), 3.40(3H, s), 3.70(3H, s), 5.13(1H, s), 5.13(1H,                   d,                                                                             J=12.0), 5.30(1H, d, J=12.0), 6.89-6.94(2H, m), 7.10-7.20(2H,                  m),                                                                            7.35-7.40(2H, m), 7.50-7.52(2H, m)                                  195        3.40(3H, s), 3.70(3H, s), 5.11(1H, s), 5.11(1H, d, J=12.0),                    5.30(1H, d, J=12.0), 6.90-7.00(3H, m), 7.25-7.38(4H, m),                       7.47-                                                                          7.51(2H, m)                                                         196        86-87° C.                                                    197        91-92° C.                                                    198        2.81(3H, s), 3.35(3H, s), 5.00(1H, s), 5.08(1H, d, J=12.0),                    5.48(1H, d, J=12.0), 6.80(1H, brs), 6.93-6.97(3H, m), 7.25-                    7.49(6H, m)                                                         205        69-72° C.                                                    206        3.41(3H, s), 3.72(3H, s), 5, 10(1H, s), 5, 18(1H, d, J=12.0),                  5.34(1H, d, J=12.0), 6.92(1H, d, J=8.6), 6.17(1H, dd, J=9.0,                   2.4),                                                                          7.36-7.40(2H, m), 7.50-7.56(2H, m)                                  207        3.41(3H, s), 3.71(3H, s), 5.06(1H, s), 5.16(1H, d, J=12.0),                    5.34(1H, d, J=12.0), 7.17(1H, m), 7.22-7.30(2H, m),                            7.38-7.42(3H,                                                                  m), 7.47-7.52(2H, m)                                                208        3.39(3H, s), 3.70(3H, s), 3.77(3H, s), 5.04(1H, d, J=12.0),                    5.11(1H, s), 5.24(1H, d, J=12.0), 6.80-6.88(2H, m),                            6.90-6.95(2H,                                                                  m), 7.30-7.40(2H, m), 7.45-7.55(2H, m)                              209        2.29(3H, s), 3.39(3H, s), 3.70(3H, s), 5.07(1H, d, J=12.0),                    5.11(1H, s), 5.27(1H, d, J=12.0), 6.89(2H, d, J=18.6),                         7.09(1H, t,                                                                    J=8.6), 7.30-7.40(2H, m), 7.45-7.51(2H, m)                          210        2.34(3H, s), 3.40(3H, s), 3.70(3H, s), 5.08(1H, d, J=12.0),                    5.11(1H, s), 5.28(1H, d, J=12.0), 6.89(2H, d, J=8.6), 6.91(1H,                 s),                                                                            7.18(1H, t, J=8.0), 7.32-7.40(2H, m), 7.45-7.55(2H, m)              211        98-100° C.                                                   212        2.33(3H, s), 2.82(3H, d, J=4.8), 3.35(3H, s), 5.00(1H, s),                     5.04(1H,                                                                       d, J=12.0), 5.48(1H, d, J=12.0), 6.75-6.81(3H, m), 7.17(1H,                    t,                                                                             J=7.3), 7.30-7.46(4H, m)                                            213        2.82(3H, d, J=4.8), 3.36(3H, s), 4.94(1H, s), 5.05(1H, d,                      J=12.0),                                                                       5.47(1H, d, J=12.0), 6.80(1H, brs), 6.89(2H, d, J=1.2),                        6.96(1H, t,                                                                    J=1.2), 7.33-7.47(4H, m)                                            214        2.82(3H, d, J=4.8), 3.36(3H, s), 4.98(1H, s), 5.13(1H, d,                      J=12.0),                                                                       5.53(1H, d, J=12.0), 6.81(1H, brs), 7.15-7.26(3H, m), 7.33-                    7.50(5H, m)                                                         215        2.81(3H, d, J=4.8), 3.35(3H, s), 3.76(3H, s), 5.01(1H, s),                     5.03(1H,                                                                       d, J=12.0), 5.42(1H, d, J=12.0), 6.81(1H, brs), 6.81-6.84(2H,                  m),                                                                            6.86-6.89(2H, m), 7.30-7.48(4H, m)                                  216        2.18(3H, s), 2.28(3H, s), 3.40(3H, s), 3.70(3H, s), 5.11(1H,                   d, J=                                                                          12.2), 5.13(1H, s), 5.28(1H, d, J=12.2), 6.81(2H, d, J=7.8),                   7.08(1H, t, J=7.8), 7.35-7.38(2H, m), 7.51-7.54(2H, m)              217        2.16(3H, s), 2.27(3H, s), 2.82(3H, d, J=4.9), 3.35(3H, s),                     5.02(1H,                                                                       s), 5.04(1H, d, J=11.6), 5.44(1H, d, J=11.6), 6.80(1H, d,                      J=7.9),                                                                        6.82(1H, brs), 6.84(1H, d, J=7.9), 7.05(1H, t, J=7.9), 7.30-                   7.40(3H, m), 7.49-7.52(1H, m)                                       218        2.23(3H, s), 2.27(3H, s), 3.39(3H, s), 3.70(3H, s), 5.10(1H,                   d,                                                                             J=12.2), 5.11(1H, s), 5.27(1H, d, J=12.2), 6.81(1H, d,                         J=7.8),                                                                        6.95(1H, d, J=7.8), 6.98(1H, s), 7.34-7.38(2H, m),                             7.50-7.54(2H,                                                                  m)                                                                  219        104-106° C.                                                  221        2.17(3H, s), 2.19(3H, s), 2.81(3H, d, J=4.9), 3.35(3H, s),                     5.00(1H                                                                        s), 5.02(1H, d, J=12.2), 5.42(1H, d, J=12.2), 6.75(1H, dd,                     J=7.9,                                                                         2.4), 6.80(1H, d, J=2.4), 6.83(1H, brs), 7.02(1H, d, J=7.9)                    7.30-                                                                          7.50(4H, m)                                                         223        2.29(6H, s), 2.82(3H, d, J=4.9), 3.36(3H, s), 5.00(1H, s),                     5.02(1H,                                                                       d, J=11.0), 5.44(1H, d, J=11.0), 6.63(3H, s), 6.82(1H, brs),                   7.29-                                                                          7.48(4H, m)                                                         231        2.82(3H, d, J=4.9), 3.35(3H, s), 4.97(1H, s), 5.04(1H, d,                      J=12.0),                                                                       5.47(1H, d, J=12.0), 6.84(1H, brs), 6.85(1H, dd, J=7.4, 1.8),                  6.95(1H, dd, J=7.4, 1.8), 6.99(1H, t, J=1.8), 7.20(1H, t,                      J=7.4),                                                                        7.33-7.45(4H, m)                                                    233        87-88° C.                                                    245        2.81(3H, d, J=4.9), 3.37(3H, s), 3.85(3H, s), 5.06(1H, s),                     5.20(1H,                                                                       d, J=12.2), 5.37(1H, d, J=12.2), 6.85(1H, brs), 6.96-7.03(4H,                  m),                                                                            7.30-7.35(2H, m), 7.44-7.49(2H, m)                                  262        121-123° C.                                                  263        2.23(3H, s), 3.40(3H, s), 3.70(3H, s), 5.08(1H, s), 5.12(1H,                   d, J=                                                                          12.2), 5.27(1H, d, J=12.2), 6.83(1H, d, J=7.9), 7.10(1H, dd,                   J=7.3,                                                                         2.4), 7.33-7.39(2H, m), 7.42-7.55(2H, m)                            267        97-99° C.                                                    282        2.30(3H, s), 2.80(3H, d, J=4.9), 3.36(3H, s), 3.83(3H, s),                     5.06(1H,                                                                       s), 5.17(1H, d, J=12.2), 5.32(1H, d, J=12.2), 6.73-6.80(2H,                    m),                                                                            6.87(1H, brs), 6.89(1H, d, J=7.9), 7.30-7.35(2H, m),                           7.42-7.48(2H,                                                                  m)                                                                  285        3.40(3H, s), 3.64(3H, s), 5.18(1H, s), 6.87-6.93(3H, m), 7.11                  (1H, d, J=7.3), 7.26-7.33(3H, m), 7.51(1H, dd, J=7.3, 1.8)          286        2.81(3H, d, J=4.9), 3.33(3H, s), 4.99(1H, s), 6.85(1H, brs),                   6.86                                                                           (1H, d, J=8.6), 6.94-6.98(2H, m), 7.14(1H, t, J=7.3),                          7.26-7.36                                                                      (4H, m)                                                             288        2.33(3H, s), 3.41(3H, s), 3.68(3H, s), 5.26(1H, s),                            6.83-6.91(3H,                                                                  m), 7.11-7.15(3H, m), 7.23-7.28(1H, m), 7.48(1H, dd, J=8.0,                    1.8)                                                                289        2.32(3H, s), 2.82(3H, d, J=4.9), 3.35(3H, s), 5.04(1H, s),                     6.82                                                                           (1H, brs), 6.84(1H, d, J=8.6), 6.91-6.94(2H, m),                               7.08-7.15(3H,                                                                  m), 7.20-7.26(1H, m), 7.34(1H, dd, J=7.3, 1.8)                      291        2.23(6H, s), 3.4(3H, s), 3.68(3H, s), 5.26(1H, s),                             6.71-6.74(1H,                                                                  m), 6.80-6.86(2H, m), 7.05-7.13(2H, m), 7.22-7.28(1H, m),                      7.48(1H, dd, J=7.3, 1.8)                                            292        2.22(6H, s), 2.83(3H, d, J=4.9), 3.36(3H, s), 5.04(1H, s),                     6.73-                                                                          6.86(4H, m), 7.05-7.10(2H, m), 7.20-7.25(1H, m), 7.34(1H,                      dd, J=7.3, 1.8)                                                     293        3.40(3H, s), 3.71(3H, s), 5.19(1H, s), 5.49(1H, d, J=12.2),                    5.67                                                                           (1H, d, J=12.2), 6.85(1H, d, J=8.6), 7.35-7.39(2H, m),                         7.49-7.53                                                                      (2H, m), 7.79(1H, dd, J=7.3, 1.8), 8.46(1H, s)                      294        2.32(3H, s), 3.40(3H, s), 3.67(3H, s), 5.23(1H, s),                            6.76-6.90(4H,                                                                  m), 7.11-7.30(2H, m), 7.49(1H, dd, J=7.3, 1.8)                      295        2.32(3H, s), 2.82(3H, d, J=4.9), 3.35(3H, s), 5.03(1H, s),                     6.80-                                                                          6.91(5H, m), 7.10-7.28(3H, m), 7.34(1H, dd, J=7.3, 1.8)             296        2.27(6H, s), 3.40(3H, s), 3.67(3H, s), 5.23(1H, s), 6.61(2H,                   s),                                                                            6.74(1H, s), 6.88(1H, d, J=8.6), 7.13(1H, t, J=8.0),                           7.24-7.28(1H,                                                                  m), 7.49(1H, dd, J=7.3, 1.8)                                        297        2.27(6H, s), 2.83(3H, d, J=4.9), 3.35(3H, s), 5.02(1H, s),                     6.65(2H,                                                                       s), 6.73(1H, s), 6.75(1H, brs), 6.86(1H, d, J=8.0),                            7.06-7.09(1H,                                                                  m), 7.21-7.28(1H, m), 7.34(1H, dd, J=7.3, 1.8)                      328        2.28(3H, s), 3.40(3H, s), 3.67(3H, s), 5.18(1H, s),                            6.73-6.77(1H,                                                                  m), 6.86-6.89(2H, m), 7.19(1H, d, J=7.3), 7.25-7.30(2H, m),                    7.51(1H, dd, J=7.3, 1.8)                                            329        2.33(3H, s), 2.82(3H, d, J=4.9), 3.34(3H, s), 4.99(1H, s),                     6.77-                                                                          6.93(4H, m), 7.12(1H, t, J=7.3), 7.24-7.36(3H, m)                   358        2.17(3H, s), 2.34-2.36(3H in total), 2.44-2.63(3H in total),                   3.78-                                                                          3.81(3H in total), 4.98-5.22(3H in total), 6.71-7.81(7H in                     total)                                                              359        122-124° C.                                                  362        2.16(3H, s), 2.35(3H, s), 2.39(3H, s), 2.82(3H, d, J=4.9),                     4.36(1H,                                                                       s), 5.13(1H, d, J=11.0), 5.25(1H, d, J=11.0), 6.73(1H, d,                      J=7.3),                                                                        6.84(1H, s), 7.04(1H, d, J=7.3), 7.07(1H, brs), 7.29-7.49(4H,                  m)                                                                  366        2.26(3H, s), 2.28(3H, s), 2.79(3H, d, J=4.9), 3.36(3H, s),                     4.06(1H,                                                                       d, J=12.2), 4.69(1H, d, J=12.2), 5.18(1H, s), 6.84(1H, brs),                   6.91(1H, d, J=7.3), 7.04(1H, d, J=7.3), 7.14(1H, s),                           7.18-7.28(3H,                                                                  m), 7.36(1H, d, J=7.3)                                              372        1.56(3H, s), 2.22(3H, s), 3.23(3H, d, J=4.9), 3.35(3H, s),                     5.15(1H,                                                                       d, J=12.2), 5.36(1H, s), 5.58(1H, d, J=12.2), 6.88(1H, d,                      J=7.9),                                                                        7.11(1H, d, J=7.9), 7.13(1H, s), 7.29-7.37(3H, m),                             7.45-7.48(1H,                                                                  m), 8.75(1H, brs)                                                   413        2.83(3H, d, J=4.9), 3.36(3H, s), 5.09(1H, s), 5.50(1H, d,                      J=13.0),                                                                       5.86(1H, d, J=13.0), 6.80(1H, s), 6.85(1H, brs), 7.32-7.38(3H,                 m),                                                                            7.45-7.49(1H, m), 8.57(1H, s)                                       417        115-117° C.                                                  420        131-133° C.                                                  421        2.84(3H, d, J=4.9), 4.99(1H, brs), 5.39(1H, s), 5.57(1H, d,                    J=12.2), 5.67(1H, d, J=12.2), 6.50(1H, brs), 7.00(1H, dd,                      J=6.7,                                                                         6.1), 7.31-7.37(3H, m), 7.49-7.51(1H, m), 7.90(1H, dd, J=6.1,                  1.8), 8.27(1H, dd, J=6.7, 1.8)                                      422        63-64° C.                                                    423        105-107° C.                                                  427        133-135° C.                                                  429        79-81° C.                                                    430        3.40(3H, s), 3.71(3H, s), 5.19(1H, s), 5.49(1H, d, J=12.2),                    5.67(1H, d, J=12.2), 6.85(1H, d, J=8.6), 7.35-7.39(2H, m),                     7.46-                                                                          7.52(2H, m), 7.80(1H, dd, J=8.6, 1.8), 8.46(1H, s)                  432        3.42(3H, s), 3.70(3H, s), 5.25(1H, s), 5.49(1H, d, J=12.2),                    5.66(1H, d, J=12.2), 7.34-7.38(2H, m), 7.52-7.56(2H, m),                       7.65(1H,                                                                       d, J=2.4), 8.01(1H, d, J=2.4)                                       433        114-115° C.                                                  434        58-60° C.                                                    436        102-104° C.                                                  437        2.82(3H, d, J=5.5), 3.39(3H, s), 5.03(1H, s), 5.22(1H, d,                      J=12.0),                                                                       5.64(1H, d, J=12.0), 6.82(1H, brs), 7.19(1H, dd, J=8.0, 4.8),                  7.33-                                                                          7.49(5H, m), 8.01(1H, dd, J=4.8, 1.8)                               439        2.09(3H, s), 2.34(3H, s), 3.85(3H, s), 5.05(1H, d, J=11.0),                    5.10(1H, d, J=11.0), 6.68(1H, s), 6.74(1H, d, J=7.3), 6.75(1H,                 s),                                                                            7.03(1H, d, J=7.3), 7.48-7.53(2H, m), 7.61-7.66(1H, m)              443        89-90° C.                                                    448        80-82° C.                                                    453        83-85° C.                                                    454        3.39(3H, s), 3.70(3H, s), 5.19(1H, s), 5.38(1H, d, J=12.2),                    5.58(1H, d, J=12.2), 6.73(1H, d, J=9.1), 7.30-7.37(2H, m),                     7.47-                                                                          7.55(3H, m), 8.11(1H, d, J=2.4)                                     459        103-105° C.                                                  461        0.87(3H, t, J=7.3), 1.26-1.40(2H, m), 1.51-1.62(2H, m),                        2.20(3H,                                                                       s), 2.31(3H, s), 3.22(3H, d, J=4.9), 3.44(2H, t, J=7.3),                       5.14(1H, d,                                                                    J=11.6), 5.46(1H, s), 5.59(1H, d, J=11.6), 6.69(1H, d,                         J=7.3),                                                                        6.80(1H, s), 7.02(1H, d, J=7.3), 7.31-7.34(3H, m), 7.47-                       7.51(1H, m), 8.82(1H, brs).                                         462        205-210° C.                                                  463        105-110° C.                                                  465        2.11(3H, s), 2.23(3H, s), 2.29(3H, s), 2.81(3H, d, J=4.9),                     3.35(3H,                                                                       s), 5.03(1H, s), 5.03(1H, d, J=11.6), 5.44(1H, d, J=11.6),                     6.64(1H,                                                                       s), 6.68(1H, s), 7.32-7.43(3H, m), 7.50-7.53(1H, m)                 466        81-82° C.                                                    467        91-92° C.                                                    468        2.83(1H, d, J=4.9), 3.38(3H, s), 4.47(1H, d, J=12.2), 4.88(1H,                 d,                                                                             J=12.2), 5.14(1H, s), 6.82(1H, brs), 7.20-7.30(2H, m), 7.32-                   7.38(1H, m), 7.42-7.49(1H, m), 7.56(1H, d, J=1.8), 8.35(1H,                    d,                                                                             J=1.8)                                                              469        0.91 & 1.13(3H in total, each s), 2.21(3H, s), 2.85 & 2.95(3H                  in                                                                             total, each s), 3.26 & 3.48(2H in total, each m), 3.43(3H, s),                 5.05(1H,                                                                       d, J=12.2), 5.22(1H, s), 5.25(1H, d, J=12.2), 6.86(1H, d,                      J=9.1),                                                                        7.12(1H, d, J=7.3), 7.13(1H, s), 7.33-7.41(3H, m),                             7.49-7.55(1H,                                                                  m)                                                                  470        2.18(3H, s), 2.32(3H, s), 3.41(3H, s), 5.05(1H, d, J=11.6),                    5.17(1H, s), 5.31(1H, d, J=11.6), 6.71(1H, d, J=7.3), 6.76(1H;                 s),                                                                            7.02(1H, d, J=7.9), 7.35-7.41(2H, m), 7.48-7.54(2H, m)              471        2.27(3H, s), 3.22(3H, s), 3.49(3H, s), 3.54(3H, s), 5.09(1H,                   d, J=                                                                          12.2), 5.26(1H, d, J=12.2), 5.72(1H, s), 6.86-6.94(2H, m),                     7.15-                                                                          7.20(2H, m), 7.25-7.39(3H, m), 7.56(1H, d, J=7.3)                   472        110-112° C.                                                  473        2.28(6H, s), 2.80(3H, d, J=4.9), 3.33(3H, s), 4.87(1H, d,                      J=12.2),                                                                       5.06(1H, s), 5.27(1H, d, J=12.2), 6.77(1H, brs), 6.98(1H, dd,                  J=8.5, 6.1), 7.02(2H, d, J=7.3), 7.30-7.43(3H, m),                             7.60-7.63(1H,                                                                  m)                                                                  __________________________________________________________________________

Example 19 Synthesis of (E)-2-benzylideneaminooxymethyl-(α-methoxy-N-methylphenylacetamide (Compound 480)

A solution of 2-hydroxymethyl-α-methoxy-N-methyl-phenylacetamide (0.42 g, 2.0 mmol) in tetrahydrofuran (4 ml) was stirred at 0° C., and thionyl chloride (0.17 ml, 2.4 mmol) and one drop of N,N-dimethylformamide were added. The mixture was stirred at room temperature for 2 hours, and water was added. The resulting mixture was extracted with ether, washed with saturated brine and dried over anhydrous magnesium sulfate. Evaporation of the solvent gave a crude product (0.38 g) as an oil. Benzaldehyde oxime (0.37 g, 3.1 mmol) and potassium carbonate (0.55 g, 4.0 mmol) were added to a solution of the crude product in N,N-dimethylformamide (6 ml), and the mixture was stirred at room temperature for 3 days. Water was added, and the mixture was extracted with ether and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=13/7) to give the desired compound (E)-2-benzylideneaminooxymethyl-α-methoxy-N-methylphenylacetamide (0.32 g, 51%) as white crystals.

mp.: 75.0-75.5° C.

NMR (δ ppm, TMS/CDCl₃): 2.84(3H,d,J=4.9), 3.34 (3H,s), 5.13(1H,s), 5.23(1H,d,J=12.2), 5.65(1H,d,J=12.2), 6.80 (1H,brs), 7.27-7.40(6H,m), 7.41-7.48(1H,m), 7.53-7.58(2H,m), 8.10(1H,s).

Example 20 Synthesis of methyl (E)-2-benzylideneaminooxymethyl-α-hydroxyphenylacetate (Compound No. 483)

Sodium borohydride (0.04 g, 1.0 mmol) was added to a solution of methyl 2-(2-bromomethyl)phenyl-2-oxoacetate (0.51 g, 2.0 mmol) in methanol (10 ml). After 8 minutes, acetic acid was added to decompose the excess reagent. Water was added, and the mixture was extracted with ethyl acetate and dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=4/1) to give the desired compound methyl 2-bromomethyl-α-hydroxy-phenylacetate (0.41 g, 80%) as an oil.

Then, benzaldehyde oxime (0.28 g, 2.3 mmol) and potassium carbonate (0.43 g, 3.1 mmol) were added to a solution of methyl 2-bromomethyl-α-hydroxyphenylacetate (0.40 g, 1.5 mmol) in acetone (6 ml), and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted with ether, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=3/1) to give the desired compound methyl (E)-2-benzylideneaminooxymethyl-α-hydroxy-phenylacetate (0.08 g, 17%) as an oil.

NMR (δ ppm, TMS/CDCl₃): 3.74(1H,d,J=5.5), 3.75 (3H,s), 5.31(1H,d,J=12.2), 5.42(1H,d,J=12.2), 5.59 (1H,d,J=5.5), 7.34-7.39(6H,m), 7.41-7.50(1H,m), 7.52-7.66 (2H,m), 8.11(1H,s).

Example 21 Synthesis of methyl (E)-2-(2-benzylideneaminooxy-methyl)phenyl-2-oxoacetate

Benzaldehyde oxime (2.13 g, 17.6 mmol) and potassium carbonate (2.90 g, 21.0 mmol) were added a solution of methyl 2-(2-bromomethyl)phenyl-2-oxoacetate (3.00 g, 11.7 mmol) in acetone (10 ml), and the mixture was stirred at room temperature for 7 hours. Water was added, and the mixture was extracted with ether and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=17/3) to give the desired compound methyl (E)-2-(benzylideneaminooxymethyl)-2-oxophenylacetate (2.39 g, 69%).

NMR (δ ppm, TMS/CDCl₃): 3.89(3H,s), 5.32 (1H,d,J=12.2), 5.40(1H,d,J=12.2), 7.32-7.59(8H,m), 7.70 (1H,d,J=6.7), 8.16(1H,s).

Example 22 Synthesis of methyl (E)-α-hydroxy-2-(α-methyl-4-chlorobenzylideneaminooxymethyl)phenylacetate (Compound No. 479)

A solution of methyl 2-bromomethyl-α-hydroxyphenylacetate (30.53 g, 0.118 mmol) and 3,4-dihydro-2H-pyran (17.84 g, 0.212 mol) in methylene chloride (230 ml) was stirred at 0° C. Pyridinium p-toluenesulfonate (2.96 g, 0.012 mol) was added, and the mixture was stirred at room temperature for 2 hours. Water was added, and the mixture was extracted with methylene chloride and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=17/3) to give the desired compound methyl 2-bromomethyl-α-(tetrahydropyran-2-yl)phenylacetate (33.58 g, 83.0%) as an oil.

Then, a solution of methyl 2-bromomethyl-α-(tetrahydropyran-2-yl)phenylacetate (4.00 g, 11.7 mmol) and 4-chloroacetophenone oxime (2.97 g, 17.5 mmol) in N,N-dimethylformamide (30 ml) was stirred at 0° C., and 60% oily sodium hydride (0.70 g, 17.5 mmol) was added thereto. After 2 hours, water was added, and the mixture was adjusted to pH 7 with 1N hydrochloric acid, extracted with ether and dried over anhydrous magnesium sulfate. Evaporation of the solvent gave a crude product (6.28 g).

The crude product was dissolved in methanol (35 ml), and pyridinium p-toluenesulfonate (0.29 g, 1.2 mmol) was added. After heating under reflux for 30 minutes, the reaction mixture was concentrated under reduced pressure, and water was added. The mixture was extracted with ether and dried over anhydrous magnesium sulfate, and the solvent was evaporated. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=3/1) to give the desired compound methyl (E)-α-hydroxy-2-(α-methyl-4-chlorobenzylideneaminooxy)phenylacetate (2.75 g, 68%) as an oil.

NMR (δ ppm, TMS/CDCl₃): 2.23(3H,s), 3.75(3H,s), 3.77 (1H,d,J=5.5), 5.34(1H,d,J=12.2), 5.42(1H,d,J=12.2), 7.29-7.38(5H,m), 7.43-7.48(1H,m), 7.56(2H,d,J=8.6).

Example 23 Synthesis of methyl (E)-α-methoxy-2-(α-methyl-4-chlorobenzylideneaminooxy)phenylacetate (Compound No. 477)

60% oily sodium hydride (0.20 g, 5.0 mmol) was added to a solution of methyl (E)-α-hydroxy-2-(α-methyl-4-chlorobenzylideneaminooxy)phenylacetate (1.59 g, 4.6 mmol) and methyl iodide (1.95 g, 13.7 mmol) in N,N-dimethylformamide (15 ml) with stirring at 0° C. After 45 minutes, water was added, and the mixture was adjusted to pH 1 with 1N hydrochloric acid, extracted with ether, washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane/methylene chloride=9/1) to give the desired compound methyl (E)-α-methoxy-2-(α-methyl-4-chlorobenzylideneaminooxy)phenylacetate (1.19 g, 72%) as an oil.

NMR (δ ppm, TMS/CDCl₃): 2.23(3H,s), 3.39(3H,s), 3.71 (3H,s), 5.24(1H,s), 5.27(1H,d,J=12.2), 5.51(1H,d,J=12.2), 7.30-7.54(6H,m), 7.58(2H,d,J=8.5).

Example 24 Synthesis of (E)-α-methoxy-N-methyl-2-(α-methyl-4-chlorobenzylideneaminooxy)phenylacetamide (Compound No. 474)

A solution of methyl (E)-α-methoxy-2-(α-methyl-4-chlorobenzylideneaminooxy)phenylacetate (0.48 g, 1.3 mmol) and 40% monomethylamine--methanol solution (10 ml) was stirred in a sealed tube at 80° C. for 15 hours. The mixture was cooled to room temperature, and then the solvent was evaporated under reduced pressure. Water was added, the mixture was adjusted to pH 1 with 1N hydrochloric acid, extracted with methylene chloride and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=3/2) to give the desired compound (E)-α-methoxy-N-methyl-2-(α-methyl-4-chlorobenzylideneaminooxy)phenylacetamide (0.41 g, 86%) as an oil.

NMR (δ ppm, TMS/CDCl₃): 2.22(3H,s), 2.83 (3H,d,J=4.9), 3.32(3H,s), 5.13(1H,s), 5.26(1H,d,J=12.2), 5.66(1H,d,J=12.2), 6.77(1H,brs), 7.29-7.47(6H,m), 7.57 (2H,d,J=8.5).

Example 25 Synthesis of (E)-α-methoxy-N-methyl-2-(α-methyl-4-chlorobenzylideneaminooxy)phenylthioacetamide (Compound 603)

Lawesson's reagent (40 mg, 0.1 mmol) was added to a solution of (E)-α-methoxy-N-methyl-2-(α-methyl-4-chloro-benzylideneaminooxy)phenylacetamide (73 mg, 0.2 mmol) in toluene (3 ml), and the mixture was heated at 80° C. for 1.5 hours with stirring. The mixture was cooled to room temperature. Water was added, and the mixture was extracted with ether and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=4/1) to give the desired compound (E)-α-methoxy-N-methyl-2-(α-methyl-4-chlorobenzylideneaminooxy)phenylthioacetamide (50 mg, 66%) as an oil.

NMR (δ ppm, TMS/CDCl₃): 2.23(3H,s), 3.25 (3H,d,J=4.9), 3.33(3H,s), 5.29(1H,d,J=12.2), 5.51(1H,s), 5.80 (1H,d,J=12.2), 7.25-7.36(5H,m), 7.42-7.47(1H,m), 7.58 (2H,d,J=9.2), 8.77(1H,s).

Example 26 Synthesis of ethyl α-hydroxy-2-(tetrahydropyran-2-yloxymethyl)phenylacetate

A solution of ethyl 2-oxo-2- 2-(tetrahydropyran-2-yloxymethyl)phenyl!acetate (22.60 g, 77.3 mmol) in methanol (20 ml) was stirred at 0° C., and sodium borohydride (1.46 g, 38.6 mmol) was added to thereto. After 10 minutes, water (100 ml) was added, and the mixture was extracted with ethyl acetate and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=4/1) to give the desired compound ethyl α-hydroxy-2-(tetrahydropyran-2-yloxymethyl)phenylacetate (20.47 g, 90.0%) as an oil.

NMR (δ ppm, TMS/CDCl₃): 1.19-1.22(3H,m), 1.50-1.73 (6H,m), 3.52-3.57(1H,m), 3.80 and 3.87(1H in toral, each d,J=5.5), 3.81-3.88(1H,m), 4.09-4.30(2H,m), 4.65 and 4.69 (1H in total, each d,J=12.2), 4.69(1H,m), 4.89 and 4.92(1H in total, each d,J=12.2), 5.48(1H,m), 7.30-7.41(4H,m).

Example 27 Synthesis of ethyl α-methoxy-2-(tetrahydropyran-2-yloxymethyl)phenylacetate

Methyl iodide (20.25 g, 143 mmol) was added to a solution of ethyl α-hydroxy-2-(tetrahydropyran-2-yloxymethyl)phenylacetate (14.00 g, 47.6 mmol) in N,N-dimethylformamide (40 ml), and the mixture was stirred at 0° C. 60% oily sodium hydride (1.90 g, 47.5 mmol) was added thereto. After 30 minutes, water (100 ml) was added, and the mixture was extracted with ether and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane/ ethyl acetate=4/1) to give the desired compound ethyl α-methoxy-2-(tetrahydropyran-2-yloxymethyl)phenylacetate (14.00 g, 95.5%) as an oil.

NMR (δ ppm, TMS/CDCl₃): 1.20(3H,t,J=6.8), 1.50-1.90(6H,m), 3.38 and 3.39(3H in total, each s), 3.50-3.60 (1H,m), 3.89-3.95(1H,m), 4.10-4.30(2H,m), 4.56 and 5.01(1H in total, each d,J=12.2), 4.62(1H,m), 4.74 and 4.84(1H in total, each d, J=12.2), 5.17 and 5.23(1H in total,.each s), 7.30-7.51(4H,m).

Example 28 Synthesis of 4-methoxy-3-isochromanone

Pyridinium p-toluenesulfonate (0.30 g) was added to a solution of ethyl α-methoxy-2-(tetrahydropyran-2-yloxy-methyl)phenylacetate (14.00 g, 45.4 mmol) in methanol (50 ml), and the mixture was heated under reflux for 1 hour. The mixture was cooled to room temperature, and water (50 ml) was added. The mixture was extracted with methylene chloride and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by recrystallization from n-hexane/ethyl acetate (=1/1) to give the desired compound 4-methoxy-3-isochromanone (6.00 g, 74.2%) as white crystals.

mp.: 82-86° C.

NMR (δ ppm, TMS/CDCl₃): 3.73(3H,s), 4.75(1H,s), 5.28 (1H,d,J=14.0), 5.38(1H,d,J=14.0), 7.24-7.27(1H,m), 7.37(2H,m), 7.56(1H,d,J=7.3).

Example 29 Synthesis of 2-hydroxymethyl-α-methoxy-N-methyl-phenylacetamide

40% methylamine--methanol solution (9.80 g, 126 mmol) was added to 4-methoxy-3-isochromanone (7.50 g, 42.1 mmol) in methanol (40 ml), and the mixture was stirred at room temperature for 1 hour. Evaporation of the solvent gave the desired compound 2-hydroxymethyl-(α-methoxy-N-methylphenyl-acetamide (8.50 g, 96.5%) as white crystals.

mp.: 80-82° C.

NMR (δ ppm, TMS/CDCl₃): 2.86(3H,s), 3.35(3H,s), 4.47 (1H,d,J=11.6), 4.88(1H,d,J=11.6), 5.08(1H,s), 6.98(1H,brs), 7.32-7.41(4H,m).

Example 30 Synthesis of (E)-α-methoxy-2-(α-methyl-4-chloro-benzylideneaminooxymethyl)phenylacetic acid (Compound No. 637)

1N sodium hydroxide solution (10 ml) was added to a solution of ethyl (E)-(α-methoxy-2-(α-methyl-4-chloro-benzylideneaminooxymethyl)phenylacetate (0.70 g, 1.9 mmol) in methanol (10 ml), and the mixture was stirred at room temperature for 2 hours. The mixture was adjusted to pH 4 with 1N hydrochloric acid, extracted with methylene chloride and dried over anhydrous magnesium sulfate. Evaporation of the solvent gave the desired compound (E)-α-methoxy-2-(α-methyl-4-chlorobenzylideneaminooxymethyl)phenylacetic acid (0.50 g, 77%) as an oil.

NMR (δ ppm, TMS/CDCl₃): 2.20(3H,s), 3.39(3H,s), 5.25 (1H,s), 5.25(1H,d,J=12.2), 5.52(1H,d,J=12.2), 7.30-7.57(8H,m).

Example 31

According to the same manner as that described in Examples 19 to 30, various compounds of the formula (I) were synthesized. The compounds thus obtained and the physical data of their representative compounds are shown below. In the tables, the compounds obtained in Examples 19 to 30 and their physical data are also listed.

In the tables, Compound Nos. 474-935 are compounds of the formula (I) wherein M is O, and Q is a group of the formula (a); Compounds Nos. 936-980 are compounds of the formula (I) wherein M is NR², and Q is a group of the formula (a); and Compound Nos. 981-1010 are compounds of the formula (I) wherein Q is a group of the formula (b).

    __________________________________________________________________________     Comp.                                                                          No.   X  R.sup.1                                                                             Y     Z  n  R.sup.12                                                                             R.sup.13                                       __________________________________________________________________________     474   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             4-Cl-phenyl                                    475   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             4-Cl-phenyl                                    476   H  OCH.sub.3                                                                           NH.sub.2                                                                             O  1  CH.sub.3                                                                             4-Cl-phenyl                                    477   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             4-Cl-phenyl                                    478   H  OH   NH.sub.2                                                                             O  1  CH.sub.3                                                                             4-Cl-phenyl                                    479   H  OH   OCH.sub.3                                                                            O  1  CH.sub.3                                                                             4-Cl-phenyl                                    480   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  H     Phenyl                                         481   H  OH   NHCH.sub.3                                                                           O  1  H     Phenyl                                         482   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  H     Phenyl                                         483   H  OH   OCH.sub.3                                                                            O  1  H     Phenyl                                         484   H  OCH.sub.3                                                                           NH.sub.2                                                                             O  1  H     Phenyl                                         485   H  OH   NH.sub.2                                                                             O  1  H     Phenyl                                         486   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             Phenyl                                         487   H  OCH.sub.3                                                                           NH.sub.2                                                                             O  1  CH.sub.3                                                                             Phenyl                                         488   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             Phenyl                                         489   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             Phenyl                                         490   H  OH   NH.sub.2                                                                             O  1  CH.sub.3                                                                             Phenyl                                         491   H  OH   OCH.sub.3                                                                            O  1  CH.sub.3                                                                             Phenyl                                         492   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             4-OCH.sub.3 -phenyl                            493   H  OCH.sub.3                                                                           NH.sub.2                                                                             O  1  CH.sub.3                                                                             4-OCH.sub.3 -phenyl                            494   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             4-OCH.sub.3 -phenyl                            495   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             4-OCH.sub.3 -phenyl                            496   H  OH   NH.sub.2                                                                             O  1  CH.sub.3                                                                             4-OCH.sub.3 -phenyl                            497   H  OH   OCH.sub.3                                                                            O  1  CH.sub.3                                                                             4-OCH.sub.3 -phenyl                            498   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             4-CH.sub.3 -phenyl                             499   H  OCH.sub.3                                                                           NH.sub.2                                                                             O  1  CH.sub.3                                                                             4-CH.sub.3 -phenyl                             500   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             4-CH.sub.3 -phenyl                             501   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             4-CH.sub.3 -phenyl                             502   H  OH   NH.sub.2                                                                             O  1  CH.sub.3                                                                             4-CH.sub.3 -phenyl                             503   H  OH   OCH.sub.3                                                                            O  1  CH.sub.3                                                                             4-CH.sub.3 -phenyl                             504   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             2,4-Cl.sub.2 -phenyl                           505   H  OCH.sub.3                                                                           NH.sub.2                                                                             O  1  CH.sub.3                                                                             2,4-Cl.sub.2 -phenyl                           506   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             2,4-Cl.sub.2 -phenyl                           507   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             2,4-Cl.sub.2 -phenyl                           508   H  OH   NH.sub.2                                                                             O  1  CH.sub.3                                                                             2,4-Cl.sub.2 -phenyl                           509   H  OH   OCH.sub.3                                                                            O  1  CH.sub.3                                                                             2,4-Cl.sub.2 -phenyl                           510   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             2-Cl-phenyl                                    511   H  OH   NH.sub.2                                                                             O  1  CH.sub.3                                                                             2-Cl-phenyl                                    512   H  OH   OCH.sub.3                                                                            O  1  CH.sub.3                                                                             2-Cl-phenyl                                    513   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             2-Cl-phenyl                                    514   H  OCH.sub.3                                                                           NH.sub.2                                                                             O  1  CH.sub.3                                                                             2-Cl-phenyl                                    515   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             2-Cl-phenyl                                    516   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             3-Cl-phenyl                                    517   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             3-Cl-phenyl                                    518   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             3-Cl-phenyl                                    519   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             2-CF.sub.3 -phenyl                             520   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             2-CF.sub.3 -phenyl                             521   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             2-CF.sub.3 -phenyl                             522   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             3-CF.sub.3 -phenyl                             523   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             3-CF.sub.3 -phenyl                             524   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             3-CF.sub.3 -phenyl                             525   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             4-CF.sub.3 -phenyl                             526   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             4-CF.sub.3 -phenyl                             527   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             4-CF.sub.3 -phenyl                             528   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             4-NO.sub.2 -phenyl                             529   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             4-NO.sub.2 -phenyl                             530   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             4-NO.sub.2 -phenyl                             531   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             2-CH.sub.3 -phenyl                             532   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             2-CH.sub.3 -phenyl                             533   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             2-CH.sub.3 -phenyl                             534   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             3-CH.sub.3 -phenyl                             535   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             3-CH.sub.3 -phenyl                             536   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             3-CH.sub.3 -phenyl                             537   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             4-CN-phenyl                                    538   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             4-CN-phenyl                                    539   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             4-CN-phenyl                                    540   H  OH   NHCH.sub.3                                                                           O  1  C.sub.2 H.sub.5                                                                      4-Cl-phenyl                                    541   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  C.sub.2 H.sub.5                                                                      4-Cl-phenyl                                    542   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  C.sub.2 H.sub.5                                                                      4-Cl-phenyl                                    543   H  OH   NHCH.sub.3                                                                           O  1  C.sub.2 H.sub.5                                                                      4-OCH.sub.3 -phenyl                            544   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  C.sub.2 H.sub.5                                                                      4-OCH.sub.3 -phenyl                            545   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  C.sub.2 H.sub.5                                                                      4-OCH.sub.3 -phenyl                            546   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             CH.sub.3                                       547   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             CH.sub.3                                       548   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             CH.sub.3                                       549   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3, C.sub.4 H.sub.9 EZ mixture                 550   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3, C.sub.4 H.sub.9 EZ mixture                 551   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3, C.sub.4 H.sub.9 EZ mixture                 552   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             2-OCH.sub.3 -phenyl                            553   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             2-OCH.sub.3 -phenyl                            554   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             2-OCH.sub.3 -phenyl                            555   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             3-OCH.sub.3 -phenyl                            556   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             3-OCH.sub.3 -phenyl                            557   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             3-OCH.sub.3 -phenyl                            558   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             3,4-(CH.sub.3).sub.2 -phenyl                   559   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             3,4-(CH.sub.3).sub.2 -phenyl                   560   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             3,4-(CH.sub.3).sub.2 -phenyl                   561   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             3,4-Cl.sub.2 -phenyl                           562   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             3,4-Cl.sub.2 -phenyl                           563   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             3,4-Cl.sub.2 -phenyl                           564   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             3-CH.sub.3 -4-OCH.sub.3 -phenyl                565   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             3-CH.sub.3 -4-OCH.sub.3 -phenyl                566   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             3-CH.sub.3 -4-OCH.sub.3 -phenyl                567   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             3-Cl-4-CH.sub.3 -phenyl                        568   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             3-Cl-4-CH.sub.3 -phenyl                        569   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             3-Cl-4-CH.sub.3 -phenyl                        570   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             COCH.sub.3                                     571   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             COCH.sub.3                                     572   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             COCH.sub.3                                     573   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             CO-phenyl                                      574   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             CO-phenyl                                      575   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             CO-phenyl                                      576   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             4-Biphenylyl                                   577   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             4-Biphenylyl                                   578   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             4-Biphenylyl                                   579   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             1-Naphthyl                                     580   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             1-Naphthyl                                     581   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             1-Naphthyl                                     582   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             2-Furyl                                        583   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             2-Furyl                                        584   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             2-Furyl                                        585   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             2-Thienyl                                      586   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             2-Thienyl                                      587   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             2-Thienyl                                      588   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             2-Pyridyl                                      589   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             2-Pyridyl                                      590   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             2-Pyridyl                                      591   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             2-Pyrazinyl                                    592   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             2-Pyrazinyl                                    593   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             2-Pyrazinyl                                    594   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             2-Pyrimidinyl                                  595   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             2-Pyrimidinyl                                  596   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             2-Pyrimidinyl                                  597   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             5-CF.sub.3 -pyridin-2-yl                       598   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             5-CF.sub.3 -pyridin-2-yl                       599   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             5-CF.sub.3 -pyridin-2-yl                       600   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             4-OC.sub.2 H.sub.5 -pyrimidin-                                                 2-yl                                           601   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.3                                                                             4-OC.sub.2 H.sub.5 -pyrimidin-                                                 2-yl                                           602   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.3                                                                             4-OC.sub.2 H.sub.5 -pyrimidin-                                                 2-yl                                           603   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           S  1  CH.sub.3                                                                             4-Cl-phenyl                                    604   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CF.sub.3                                                                             4-Cl-phenyl                                    605   H  OCHF.sub.2                                                                          NHCH.sub.3                                                                           O  1  CF.sub.3                                                                             4-Cl-phenyl                                    606   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           S  1  CH.sub.3                                                                             4-OCH.sub.3 -phenyl                            607   H  OCH.sub.3                                                                           SCH.sub.3                                                                            O  1  CH.sub.3                                                                             4-OCH.sub.3 -phenyl                            608   H  OCH.sub.3                                                                           SCH.sub.3                                                                            O  1  CH.sub.3                                                                             4-Cl-phenyl                                    609   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           S  1  CH.sub.3                                                                             4-CH.sub.3 -phenyl                             610   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           S  1  CH.sub.3                                                                             4-CF.sub.3 -phenyl                             611   H  OCH.sub.3                                                                           SCH.sub.3                                                                            O  1  CH.sub.3                                                                             4-CH.sub.3 -phenyl                             612   H  OH   NHCH.sub.3                                                                           O  1  CH.sub.2 OCH.sub.3                                                                   4-Cl-phenyl                                    613   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  CH.sub.2 OCH.sub.3                                                                   4-Cl-phenyl                                    614   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  CH.sub.2 OCH.sub.3                                                                   4-Cl-phenyl                                    615   H  OH   NHCH.sub.3                                                                           O  1  C.sub.2 H.sub.5                                                                      4-CH.sub.3 -phenyl                             616   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  C.sub.2 H.sub.5                                                                      4-CH.sub.3 -phenyl                             617   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  C.sub.2 H.sub.5                                                                      4-CH.sub.3 -phenyl                             618   H  OH   NHCH.sub.3                                                                           O  1  C.sub.4 H.sub.9                                                                      4-CH.sub.3 -phenyl                             619   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  C.sub.4 H.sub.9                                                                      4-CH.sub.3 -phenyl                             620   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  C.sub.4 H.sub.9                                                                      4-CH.sub.3 -phenyl                             621   H  OH   NHCH.sub.3                                                                           O  1  C.sub.4 H.sub.9                                                                      4-Cl-phenyl                                    622   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  C.sub.4 H.sub.9                                                                      4-Cl-phenyl                                    623   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  C.sub.4 H.sub.9                                                                      4-Cl-phenyl                                    624   H  OH   NHCH.sub.3                                                                           O  1  C.sub.4 H.sub.9                                                                      4-OCH.sub.3 -phenyl                            625   H  OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1  C.sub.4 H.sub.9                                                                      4-OCH.sub.3 -phenyl                            626   H  OCH.sub.3                                                                           OCH.sub.3                                                                            O  1  C.sub.4 H.sub.9                                                                      4-OCH.sub.3 -phenyl                            __________________________________________________________________________           Comp. No.                                                                                   R.sup.1                                                                              Y                                                                                       n                                                                          1 #STR191##                                      __________________________________________________________________________     627       H  OCH.sub.3                                                                            NHCH.sub.3                                                                           O  1                                                                                2 #STR192##                                      628       H  OCH.sub.3                                                                            OCH.sub.3                                                                            O  1                                                                                3 #STR193##                                      629       H  OCH.sub.3                                                                            NHCH.sub.3                                                                           O  1                                                                                4 #STR194##                                      630       H  OCH.sub.3                                                                            OCH.sub.3                                                                            O  1                                                                                5 #STR195##                                      __________________________________________________________________________     Comp.                                                                          No. X   R.sup.1                                                                             Y    Z n R.sup.12   R.sup.13                                      __________________________________________________________________________     631 H   OCH.sub.3                                                                           OC.sub.2 H.sub.5                                                                    O 1 CH.sub.3   4-Cl-phenyl                                   632 H   OCH.sub.3                                                                           NHC.sub.2 H.sub.5                                                                   O 1 CH.sub.3   4-Cl-phenyl                                   633 H   OC.sub.2 H.sub.5                                                                    OCH.sub.3                                                                           O 1 CH.sub.3   4-Cl-phenyl                                   634 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   4-Cl-phenyl                                   635 H   OC.sub.4 H.sub.9                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   4-Cl-phenyl                                   636 H   OC.sub.4 H.sub.9                                                                    OCH.sub.3                                                                           O 1 CH.sub.3   4-Cl-phenyl                                   637 H   OCH.sub.3                                                                           OH   O 1 CH.sub.3   4-Cl-phenyl                                   638 H   OCH.sub.3                                                                           N(CH.sub.3).sub.2                                                                   O 1 CH.sub.3   4-Cl-phenyl                                   639 H   OCOCH.sub.3                                                                         NHCH.sub.3                                                                          O 1 CH.sub.3   4-Cl-phenyl                                   640 H   OTHP NHCH.sub.3                                                                          O 1 CH.sub.3   4-Cl-phenyl                                   641 H   OTHP OCH.sub.3                                                                           O 1 CH.sub.3   4-Cl-phenyl                                   642 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           3-Cl-phenyl                                   643 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           2-Cl-phenyl                                   644 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           2-CH.sub.3 -phenyl                            645 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           3-CH.sub.3 -phenyl                            646 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           2-OCH.sub.3 -phenyl                           647 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           3-OCH.sub.3 -phenyl                           648 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 2 CH.sub.3   4-Cl-phenyl                                   649 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 2 CH.sub.3   4-CH.sub.3 -phenyl                            650 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 2 CH.sub.3   4-OCH.sub.3 -phenyl                           651 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 2 CH.sub.3   4-CF.sub.3 -phenyl                            652 5-Cl                                                                               OH   NHCH.sub.3                                                                          O 1 CH.sub.3   4-Cl-phenyl                                   653 5-CH.sub.3                                                                         OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   4-Cl-phenyl                                   654 5-OCH.sub.3                                                                        OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 CH.sub.3   4-Cl-phenyl                                   655 5-Cl                                                                               OH   NHCH.sub.3                                                                          O 1 CH.sub.3   4-OCH.sub.3 -phenyl                           656 5-CH.sub.3                                                                         OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   4-OCH.sub.3 -phenyl                           657 5-OCH.sub.3                                                                        OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 CH.sub.3   4-OCH.sub.3 -phenyl                           658 5-Cl                                                                               OH   NHCH.sub.3                                                                          O 1 CH.sub.3   2-Pyridyl                                     659 5-CH.sub.3                                                                         OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   2-Pyridyl                                     66O 5-OCH.sub.3                                                                        OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 CH.sub.3   2-Pyridyl                                     661 5-Cl                                                                               OH   NHCH.sub.3                                                                          O 1 CH.sub.3   2-Pyrazinyl                                   662 5-CH.sub.3                                                                         OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   2-Pyrazinyl                                   663 5-OCH.sub.3                                                                        OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 CH.sub.3   2-Pyrazinyl                                   664 5-Cl                                                                               OH   NHCH.sub.3                                                                          O 1 CH.sub.3   4-CH.sub.3 -phenyl                            665 5-CH.sub.3                                                                         OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   4-CH.sub.3 -phenyl                            666 5-OCH.sub.3                                                                        OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 CH.sub.3   4-CH.sub.3 -phenyl                            667 5-Cl                                                                               OH   NHCH.sub.3                                                                          O 1 CH.sub.3   CH.sub.3                                      668 5-CH.sub.3                                                                         OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   CH.sub.3                                      669 5-OCH.sub.3                                                                        OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 CH.sub.3   CH.sub.3                                      670 H   OH   NHCH.sub.3                                                                          O 1 CH.sub.3, C.sub.2 H.sub.5 EZ mixture                     671 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3, C.sub.2 H.sub.5 EZ mixture                     672 H   OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 CH.sub.3, C.sub.2 H.sub.5 EZ mixture                     673 H   OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 CH.sub.3   2-Cl-4-OCH.sub.3 -phenyl                      674 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   2-Cl-4-OCH.sub.3 -phenyl                      675 H   OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 CH.sub.3   2-Cl-4-CH.sub.3 -phenyl                       676 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   2-Cl-4-CH.sub.3 -phenyl                       677 H   OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 CH.sub.3   3-Cl-4-OCH.sub.3 -phenyl                      678 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   3-Cl-4-OCH.sub.3 -phenyl                      679 H   OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 CH.sub.3   3-CH.sub.3 -4-Cl-phenyl                       680 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   3-CH.sub.3 -4-Cl-phenyl                       681 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   4-CH.sub.2 OCH.sub.3 -phenyl                  682 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   4-OCHF.sub.2 -phenyl                          683 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   2,4-(OCH.sub.3).sub.2 -phenyl                 684 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   3,4-(OCH.sub.3).sub.2 -phenyl                 685 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   2,5-(OCH.sub.3).sub.2 -phenyl                 686 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   2,4-(CH.sub.3).sub.2 -phenyl                  687 H   OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 CH.sub.3   2,4-(CH.sub.3).sub.2 -phenyl                  688 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   4-Phenoxyphenyl                               689 H   OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 CH.sub.3   2-F-4-OCH.sub.3 -phenyl                       690 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   2-F-4-OCH.sub.3 -phenyl                       691 H   OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 CH.sub.3   3-F-4-OCH.sub.3 -phenyl                       692 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   3-F-4-OCH.sub.3 -phenyl                       693 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 H          4-OCH.sub.3 -phenyl                           694 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 H          4-CH.sub.3 -phenyl                            695 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 H          4-CF.sub.3 -phenyl                            696 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   2-Br-phenyl                                   697 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   3-Br-phenyl                                   698 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   4-Br-phenyl                                   699 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   2-F-phenyl                                    700 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   3-F-phenyl                                    701 H   OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 CH.sub.3   4-F-phenyl                                    702 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   4-OC.sub.2 H.sub.5 -phenyl                    703 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   4-OC.sub.3 H.sub.7 -phenyl                    704 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   4-OC.sub.4 H.sub.9 -phenyl                    705 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   4-OCH.sub.2 CH═CH.sub.2 -phenyl           706 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   4-OCH.sub.2 C.tbd.CH-phenyl                   707 H   OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 CH.sub.3   4-C.sub.2 H.sub.5 -phenyl                     708 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   4-C.sub.3 H.sub.7 -phenyl                     709 H   OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 CH.sub.3   4-C.sub.4 H.sub.9 -phenyl                     710 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   4-C(CH.sub.3).sub.3 -phenyl                   711 H   OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 CH.sub.3   2,3,5-(CH.sub.3).sub.3 -phenyl                712 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   3,4,5-(CH.sub.3).sub.3 -phenyl                713 H   OCH.sub.3                                                                           NHC.sub.2 H.sub.5                                                                   O 1 CH.sub.3   4-F-phenyl                                    714 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   4-F-phenyl                                    715 H   OCH.sub.3                                                                           NHC.sub.2 H.sub.5                                                                   O 1 CH.sub.3   4-Br-phenyl                                   716 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   4-Br-phenyl                                   717 H   OCH.sub.3                                                                           NHC.sub.2 H.sub.5                                                                   O 1 CH.sub.3   4-CH.sub.3 -phenyl                            718 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   4-CH.sub.3 -phenyl                            719 H   OCH.sub.3                                                                           NHC.sub.2 H.sub.5                                                                   O 1 C.sub.2 H.sub.5                                                                           4-CH.sub.3 -phenyl                            720 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           4-CH.sub.3 -phenyl                            721 H   OCH.sub.3                                                                           NHC.sub.2 H.sub.5                                                                   O 1 CH.sub.3   4-OCH.sub.3 -phenyl                           722 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   4-OCH.sub.3 -phenyl                           723 H   OCH.sub.3                                                                           NHC.sub.2 H.sub.5                                                                   O 1 C.sub.2 H.sub.5                                                                           4-OCH.sub.3 -phenyl                           724 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           4-OCH.sub.3 -phenyl                           725 H   OCH.sub.3                                                                           NHC.sub.2 H.sub.5                                                                   O 1 CH.sub.3   4-CF.sub.3 -phenyl                            726 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   4-CF.sub.3 -phenyl                            727 H   OCH.sub.3                                                                           NHC.sub.2 H.sub.5                                                                   O 1 C.sub.2 H.sub.5                                                                           4-CF.sub.3 -phenyl                            728 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           4-CF.sub.3 -phenyl                            729 H   OCH.sub.3                                                                           NHC.sub.2 H.sub.5                                                                   O 1 CH.sub.3   4-OC.sub.2 H.sub.5 -phenyl                    730 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   4-OC.sub.2 H.sub.5 -phenyl                    731 H   OCH.sub.3                                                                           NHC.sub.2 H.sub.5                                                                   O 1 C.sub.2 H.sub.5                                                                           4-OC.sub.2 H.sub.5 -phenyl                    732 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           4-OC.sub.2 H.sub.5 -phenyl                    733 H   OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 C.sub.3 H.sub.7                                                                           4-Cl-phenyl                                   734 H   OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 2-Thienyl  CH.sub.3                                      735 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 2-Thienyl  CH.sub.3                                      736 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.3 H.sub.7                                                                           4-Cl-phenyl                                   737 H   OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 CH.sub.2 OCH.sub.3                                                                        Phenyl                                        738 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.2 OCH.sub.3                                                                        Phenyl                                        739 H   OCH.sub.3                                                                           NHC.sub.2 H.sub.5                                                                   O 1 C.sub.2 H.sub.5                                                                           4-Cl-phenyl                                   740 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   2,4-(CH.sub.3).sub.2 -phenyl                  741 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   3,4-(CH.sub.3).sub.2 -phenyl                  742 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   2-CH.sub.3 -4-OCH.sub.3 -phenyl               743 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   2-OCH.sub.3 -4-CH.sub.3 -phenyl               744 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   2-Cl-4-OCH.sub.3 -phenyl                      745 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           2,4-(CH.sub.3).sub.2 -phenyl                  746 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           3,4-(CH.sub.3).sub.2 -phenyl                  747 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           2-CH.sub.3 -4-OCH.sub.3 -phenyl               748 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           2-OCH.sub.3 -4-CH.sub.3 -phenyl               749 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.3 H.sub.7                                                                           2,4-(CH.sub.3).sub.2 -phenyl                  750 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.3 H.sub.7                                                                           3,4-(CH.sub.3).sub.2 -phenyl                  751 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.3 H.sub.7                                                                           2-CH.sub.3 -4-OCH.sub.3 -phenyl               752 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.3 H.sub.7                                                                           2-OCH.sub.3 -4-CH.sub.3 -phenyl               753 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   4-CH.sub.3 -phenyl                            754 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   4-OCH.sub.3 -phenyl                           755 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   4-CF.sub.3 -phenyl                            756 H   OC.sub.3 H.sub.7                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   4-Cl-phenyl                                   757 H   OC.sub.3 H.sub.7                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   4-CH.sub.3 -phenyl                            758 H   OC.sub.3 H.sub.7                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   4-OCH.sub.3 -phenyl                           759 H   OC.sub.3 H.sub.7                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   4-CF.sub.3 -phenyl                            76O H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           4-CF.sub.3 -phenyl                            761 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.3 H.sub.7                                                                           4-Cl-phenyl                                   762 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.3 H.sub.7                                                                           4-CH.sub.3 -phenyl                            763 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.3 H.sub.7                                                                           4-OCH.sub.3 -phenyl                           764 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.3 H.sub.7                                                                           4-CF.sub.3 -phenyl                            765 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          S 1 CH.sub.3   4-Cl-phenyl                                   766 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          S 1 CH.sub.3   4-CH.sub.3 -phenyl                            767 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          S 1 CH.sub.3   4-OCH.sub.3 -phenyl                           768 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          S 1 CH.sub.3   4-CF.sub.3 -phenyl                            769 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          S 1 C.sub.2 H.sub.5                                                                           4-Cl-phenyl                                   770 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          S 1 C.sub.2 H.sub.5                                                                           4-CH.sub.3 -phenyl                            771 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          S 1 C.sub.2 H.sub.5                                                                           4-OCH.sub.3 -phenyl                           772 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          S 1 C.sub.2 H.sub.5                                                                           4-CF.sub.3 -phenyl                            773 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   2,5-(CH.sub.3).sub.2 -phenyl                  774 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   2,5-(CH.sub.3).sub.2 -phenyl                  775 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           2,5-(CH.sub.3).sub.2 -phenyl                  776 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          S 1 CH.sub.3   2,5-(CH.sub.3).sub.2 -phenyl                  777 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   3,5-(CH.sub.3).sub.2 -phenyl                  778 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   3,5-(CH.sub.3).sub.2 -phenyl                  779 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          S 1 CH.sub.3   3,5-(CH.sub.3).sub.2 -phenyl                  780 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           3,5-(CH.sub.3).sub.2 -phenyl                  781 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   3-CH.sub.3 -4-OCH.sub.3 -phenyl               782 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   3-CH.sub.3 -4-OCH.sub.3 -phenyl               783 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           3-CH.sub.3 -4-OCH.sub.3 -phenyl               784 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          S 1 CH.sub.3   3-CH.sub.3 -4-OCH.sub.3 -phenyl               785 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   2-Naphthyl                                    786 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           2-Naphthyl                                    787 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          S 1 CH.sub.3   2-Naphthyl                                    788 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 CH.sub.3   2-Naphthyl                                    789 H   OCH.sub.3                                                                           SCH.sub.3                                                                           O 1 C.sub.2 H.sub.5                                                                           4-Cl-phenyl                                   790 H   OCH.sub.3                                                                           SCH.sub.3                                                                           O 1 C.sub.2 H.sub.5                                                                           4-CH.sub.3 -phenyl                            791 H   OCH.sub.3                                                                           SCH.sub.3                                                                           O 1 C.sub.2 H.sub.5                                                                           4-OCH.sub.3 -phenyl                           792 H   OCH.sub.3                                                                           SCH.sub.3                                                                           O 1 C.sub.2 H.sub.5                                                                           4-CF.sub.3 -phenyl                            793 H   Cl   NHCH.sub.3                                                                          O 1 CH.sub.3   4-Cl-phenyl                                   794 H   SCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   4-Cl-phenyl                                   795 H   SCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           4-Cl-phenyl                                   796 H   NHCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 CH.sub.3   4-Cl-phenyl                                   797 H   SCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   4-CF.sub.3 -phenyl                            798 H   NHCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 CH.sub.3   4-CF.sub.3 -phenyl                            799 H   SCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   3-CF.sub.3 -phenyl                            800 H   NHCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 CH.sub.3   3-CF.sub.3 -phenyl                            801 H   SCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   4-CH.sub.3 -phenyl                            802 H   NHCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 CH.sub.3   4-CH.sub.3 -phenyl                            803 H   SCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   4-OCH.sub.3 -phenyl                           804 H   NHCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 CH.sub.3   4-OCH.sub.3 -phenyl                           805 H   SCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   4-OCHF.sub.2 -phenyl                          806 H   NHCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 CH.sub.3   4-OCHF.sub.2 -phenyl                          807 H   Cl   NHCH.sub.3                                                                          O 1 CH.sub.3   4-NO.sub.2 -phenyl                            808 H   SCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   4-NO.sub.2 -phenyl                            809 H   SCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   3,4-(CH.sub.3).sub.2 -phenyl                  810 H   NHCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 CH.sub.3   3,4-(CH.sub.3).sub.2 -phenyl                  811 H   SCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3   3,4-Cl.sub.2 -phenyl                          812 H   NHCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 CH.sub.3   3,4-Cl.sub.2 -phenyl                          813 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  4-Cl-phenyl                                   814 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 SCH.sub.3  4-Cl-phenyl                                   815 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SC.sub.2 H.sub.5                                                                          4-Cl-phenyl                                   816 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SC.sub.4 H.sub.9                                                                          4-Cl-phenyl                                   817 H   OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 SCH.sub.3  4-Cl-phenyl                                   818 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          S 1 SCH.sub.3  4-Cl-phenyl                                   819 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  4-CH.sub.3 -phenyl                            820 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 SCH.sub.3  4-CH.sub.3 -phenyl                            821 H   OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 SCH.sub.3  4-CH.sub.3 -phenyl                            822 H   9CH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SC.sub.2 H.sub.5                                                                          4-CH.sub.3 -phenyl                            823 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          S 1 SCH.sub.3  4-CH.sub.3 -phenyl                            824 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  4-CF.sub.3 -phenyl                            825 H   OC2H.sub.5                                                                          NHCH.sub.3                                                                          O 1 SCH.sub.3  4-CF.sub.3 -phenyl                            826 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SC.sub.2 H.sub.5                                                                          4-CF.sub.3 -phenyl                            827 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          S 1 SCH.sub.3  4-CF.sub.3 -phenyl                            828 H   OCH.sub.3                                                                           OCH.sub.3                                                                           O 1 SCH.sub.3  4-CF.sub.3 -phenyl                            829 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  3-CF.sub.3 -phenyl                            830 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 SCH.sub.3  3-CF.sub.3 -phenyl                            831 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SC.sub.2 H.sub.5                                                                          3-CF.sub.3 -phenyl                            832 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          S 1 SCH.sub.3  3-CF.sub.3 -phenyl                            833 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SOCH.sub.3 4-Cl-phenyl                                   834 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SO.sub.2 CH.sub.3                                                                         4-Cl-phenyl                                   835 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SOC.sub.2 H.sub.5                                                                         4-Cl-phenyl                                   836 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SO.sub.2 C.sub.2 H.sub.5                                                                  4-Cl-phenyl                                   837 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  4-OCH.sub.3 -phenyl                           838 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  4-OCH.sub.3 -phenyl                           839 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SC.sub.2 H.sub.5                                                                          4-OCH.sub.3 -phenyl                           840 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 SCH.sub.3  4-OCH.sub.3 -phenyl                           841 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  4-OCHF.sub.2 -phenyl                          842 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SC.sub.2 H.sub.5                                                                          4-OCHF.sub.2 -phenyl                          843 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  4-OCHF.sub.2 -phenyl                          844 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 SCH.sub.3  4-OCHF.sub.2 -phenyl                          845 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  3-Cl-phenyl                                   846 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SC.sub.2 H.sub.5                                                                          3-Cl-phenyl                                   847 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  2-Cl-phenyl                                   848 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SC.sub.2 H.sub.5                                                                          2-Cl-phenyl                                   849 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  4-C.sub.2 H.sub.5 -phenyl                     850 H   OC.sub.2 H.sub.5                                                                    NHCH.sub.3                                                                          O 1 SCH.sub.3  4-C.sub.2 H.sub.5 -phenyl                     851 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SC.sub.2 H.sub.5                                                                          4-OC.sub.2 H.sub.5 -phenyl                    852 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  4-OC.sub.2 H.sub.5 -phenyl                    853 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  3,4-(CH.sub.3).sub.2 -phenyl                  854 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SC.sub.2 H.sub.5                                                                          3,4-(CH.sub.3).sub.2 -phenyl                  855 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  3-Cl-4-OCH.sub.3 -phenyl                      856 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SC.sub.2 H.sub.5                                                                          3-Cl-4-OCH.sub.3 -phenyl                      857 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  3,4-Cl.sub.2 -phenyl                          858 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SC.sub.2 H.sub.5                                                                          3,4-Cl.sub.2 -phenyl                          859 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SC.sub.2 H.sub.5                                                                          4-NO.sub.2 -phenyl                            860 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  4-NO.sub.2 -phenyl                            861 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  4-Phenoxyphenyl                               862 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SC.sub.2 H.sub.5                                                                          4-Phenoxyphenyl                               863 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  2-Furyl                                       864 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  2-Thienyl                                     865 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  2-Pyridyl                                     866 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  3-Pyridyl                                     867 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  4-Pyridyl                                     868 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  2-Pyridazinyl                                 869 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  2-Pyrimidinyl                                 870 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  5-Pyrimidinyl                                 871 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  1-Naphthyl                                    872 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 SCH.sub.3  2-Naphthyl                                    873 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3, SCH.sub.3                                      874 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3, SC.sub.2 H.sub.5                               875 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 CH.sub.3, SC.sub.4 H.sub.9                               876 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5, SCH.sub.3                               877 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5, SC.sub.2 H.sub.5                        878 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5, SC.sub.4 H.sub.9                        879 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.4 H.sub.9, SCH.sub.3                               880 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.4 H.sub.9, SC.sub.2 H.sub.5                        881 H   OCH.sub.3                                                                           NHCH.sub.3                                                                          O 1 C.sub.4 H.sub.9, SC.sub.4 H.sub.9                        882 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 CH.sub.3                                                                                  6 #STR196##                                   883 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 CH.sub.3                                                                                  7 #STR197##                                   884 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 CH.sub.3                                                                                  8 #STR198##                                   885 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 CH.sub.3                                                                                  9 #STR199##                                   886 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           0 #STR200##                                   887 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           1 #STR201##                                   888 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           2 #STR202##                                   889 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 C.sub.2 H.sub.5                                                                           3 #STR203##                                   890 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 C.sub.4 H.sub.9                                                                           4 #STR204##                                   891 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 C.sub.4 H.sub.9                                                                           5 #STR205##                                   892 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 C.sub.4 H.sub.9                                                                           6 #STR206##                                   893 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 C.sub.4 H.sub.9                                                                           7 #STR207##                                   894 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 CF.sub.3                                                                                  8 #STR208##                                   895 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 CF.sub.3                                                                                  9 #STR209##                                   896 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 CF.sub.3                                                                                  0 #STR210##                                   897 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 CF.sub.3                                                                                  1 #STR211##                                   898 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1                                                                                2 #STR212##                                                                               4-Cl-phenyl                                   899 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1                                                                                3 #STR213##                                                                               4-Cl-phenyl                                   900 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1                                                                                4 #STR214##                                                                               3-Cl-phenyl                                   901 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1                                                                                5 #STR215##                                                                               3-Cl-phenyl                                   902 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 CH.sub.3                                                                                  6 #STR216##                                   903 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 CH.sub.3                                                                                  7 #STR217##                                   904 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1                                                                                8 #STR218##                                                                               4-CH.sub.3 -phenyl                            905 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1                                                                                9 #STR219##                                                                               4-CH.sub.3 -phenyl                            906 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1                                                                                0 #STR220##                                                                               4-CF.sub.3 -phenyl                            907 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1                                                                                1 #STR221##                                                                               4-CF.sub.3 -phenyl                            908 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1                                                                                2 #STR222##                                                                               3-CF.sub.3 -phenyl                            909 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1                                                                                3 #STR223##                                                                               3-CF.sub.3 -phenyl                            910 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1                                                                                4 #STR224##                                                                               4-OCH.sub.3 -phenyl                           911 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1                                                                                5 #STR225##                                                                               4-OCH.sub.3 -phenyl                           912 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1                                                                                6 #STR226##                                                                               4-OCHF.sub.2 -phenyl                          913 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1                                                                                7 #STR227##                                                                               4-OCHF.sub.2 -phenyl                          914 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1                                                                                8 #STR228##                                                                               4-NO.sub.2 -phenyl                            915 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1                                                                                9 #STR229##                                                                               4-NO.sub.2 -phenyl                            916 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 NHCH.sub.3 4-Cl-phenyl                                   917 H OC.sub.2 H.sub.5                                                                      NHCH.sub.3                                                                          O 1 NHCH.sub.3 4-Cl-phenyl                                   918 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 NHC.sub.2 H.sub.5                                                                         4-Cl-phenyl                                   919 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 NHC.sub.4 H.sub.9                                                                         4-Cl-phenyl                                   920 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 NHCH.sub.3 4-CF.sub.3 -phenyl                            921 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 NHC.sub.2 H.sub.5                                                                         4-CF.sub.3 -phenyl                            922 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 NHCH.sub.3 3-CF.sub.3 -phenyl                            923 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 NHC.sub.2 H.sub.5                                                                         3-CF.sub.3 -phenyl                            924 H OCH.sub.3                                                                             OCH.sub.3                                                                           O 1 NHCH.sub.3 4-CH.sub.3 -phenyl                            925 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 NHC.sub.2 H.sub.5                                                                         4-CH.sub.3 -phenyl                            926 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 NHCH.sub.3 4-OCH.sub.3 -phenyl                           927 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 NHC.sub.2 H.sub.5                                                                         4-OCH.sub.3 -phenyl                           928 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 NHCH.sub.3 4-OCHF.sub.2 -phenyl                          929 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 NHC.sub.2 H.sub.5                                                                         4-OCHF.sub.2 -phenyl                          930 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 NHCH.sub.3 4-NO.sub.2 -phenyl                            931 H OCH.sub.3                                                                             OCH.sub.3                                                                           O 1 NHC.sub.2 H.sub.5                                                                         4-NO.sub.2 -phenyl                            932 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 NHCH.sub.3 3,4-(CH.sub.3).sub.2 -phenyl                  933 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 NHC.sub.2 H.sub.5                                                                         3,4-(CH.sub.3).sub.2 -phenyl                  934 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 NHCH.sub.3 3,4-Cl.sub.2 -phenyl                          935 H OCH.sub.3                                                                             NHCH.sub.3                                                                          O 1 NHC.sub.2 H.sub.5                                                                         3,4-Cl.sub.2 -phenyl                          __________________________________________________________________________     Comp.                                                                          No.  X R.sup.1                                                                            Y    Z n R.sup.2                                                                               R.sup.12                                                                             R.sup.13                                      __________________________________________________________________________     936  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            CH.sub.3                                                                             0 #STR230##                                   937  H OCH.sub.3                                                                          NHCH3                                                                               O 1 COCH.sub.3                                                                            CH.sub.3                                                                             1 #STR231##                                   938  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            CH.sub.3                                                                             2 #STR232##                                   939  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            CH.sub.3                                                                             3 #STR233##                                   940  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 CH.sub.3                                                                              CH.sub.3                                                                             4-Cl-phenyl                                   941  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            CH.sub.3                                                                             4-Cl-phenyl                                   942  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COC.sub.2 H.sub.5                                                                     CH.sub.3                                                                             4-Cl-phenyl                                   943  H OCH.sub.3                                                                          NHCH.sub.3                                                                          S 1 COCH.sub.3                                                                            CH.sub.3                                                                             4-Cl-phenyl                                   944  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 CO-phenyl                                                                             CH.sub.3                                                                             4-Cl-phenyl                                   945  H OC.sub.2 H.sub.5                                                                   NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            CH.sub.3                                                                             4-Cl-phenyl                                   946  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            C.sub.2 H.sub.5                                                                      4-Cl-phenyl                                   947  H OCH.sub.3                                                                          OCH.sub.3                                                                           O 1 COCH.sub.3                                                                            CH.sub.3                                                                             4-Cl-phenyl                                   948  H OCH.sub.3                                                                          SCH.sub.3                                                                           O 1 COCH.sub.3                                                                            CH.sub.3                                                                             4-Cl-phenyl                                   949  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 CH.sub.3                                                                              CH.sub.3                                                                             4-CH.sub.3 -phenyl                            950  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            CH.sub.3                                                                             4-CH.sub.3 -phenyl                            951  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            C.sub.2 H.sub.5                                                                      4-CH.sub.3 -phenyl                            952  H OCH.sub.3                                                                          OCH.sub.3                                                                           O 1 COCH.sub.3                                                                            CH.sub.3                                                                             4-CH.sub.3 -phenyl                            953  H OCH.sub.3                                                                          SCH.sub.3                                                                           O 1 COCH.sub.3                                                                            CH.sub.3                                                                             4-CH.sub.3 -phenyl                            954  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            CH.sub.3                                                                             4-CH.sub.3 -phenyl                            955  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 CH.sub.3                                                                              CH.sub.3                                                                             4-CF.sub.3 -phenyl                            956  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            CH.sub.3                                                                             4-CF.sub.3 -phenyl                            957  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            C.sub.2 H.sub.5                                                                      4-CF.sub.3 -phenyl                            958  H OCH.sub.3                                                                          OCH.sub.3                                                                           O 1 COCH.sub.3                                                                            CH.sub.3                                                                             4-CF.sub.3 -phenyl                            959  H OCH.sub.3                                                                          SCH.sub.3                                                                           O 1 COCH.sub.3                                                                            CH.sub.3                                                                             4-CF.sub.3 -phenyl                            960  H OCH.sub.3                                                                          NHCH.sub.3                                                                          S 1 COCH.sub.3                                                                            CH.sub.3                                                                             4-CF.sub.3 -phenyl                            961  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 CH.sub.3                                                                              CH.sub.3                                                                             4-OCH.sub.3 -phenyl                           962  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            CH.sub.3                                                                             4-OCH.sub.3 -phenyl                           963  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            C.sub.2 H.sub.5                                                                      4-OCH.sub.3 -phenyl                           964  H OCH.sub.3                                                                          OCH.sub.3                                                                           O 1 COCH.sub.3                                                                            CH.sub.3                                                                             4-OCH.sub.3 -phenyl                           965  H OCH.sub.3                                                                          SCH.sub.3                                                                           O 1 COCH.sub.3                                                                            CH.sub.3                                                                             4-OCH.sub.3 -phenyl                           966  H OCH.sub.3                                                                          NHCH.sub.3                                                                          S 1 COCH.sub.3                                                                            CH.sub.3                                                                             4-OCH.sub.3 -phenyl                           967  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            CH.sub.3                                                                             3-CF.sub.3 -phenyl                            968  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            CH.sub.3                                                                             3,4-Cl.sub.2 -phenyl                          969  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            CH.sub.3                                                                             3,4-(CH.sub.3).sub.2 -phenyl                  970  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            CH.sub.3                                                                             4-OCHF.sub.2 -phenyl                          971  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            CH.sub.3                                                                             4-Phenoxyphenyl                               972  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            CH.sub.3                                                                             CH.sub.3                                      973  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            CH.sub.3                                                                             C.sub.4 H.sub.9                               974  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            COCH.sub.3                                                                           4-Cl-phenyl                                   975  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            CO-phenyl                                                                            4-Cl-phenyl                                   976  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            SCH.sub.3                                                                            4-Cl-phenyl                                   977  H OCH.sub.3                                                                          NHCH.sub.3                                                                          S 1 COCH.sub.3                                                                            SCH.sub.3                                                                            4-Cl-phenyl                                   978  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            SCH.sub.3                                                                            4-CH.sub.3 -phenyl                            979  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            SCH.sub.3                                                                            4-CF.sub.3 -phenyl                            980  H OCH.sub.3                                                                          NHCH.sub.3                                                                          O 1 COCH.sub.3                                                                            SCH.sub.3                                                                            4-OCH.sub.3 -phenyl                           __________________________________________________________________________     Comp.                                                                          No.  X  R.sup.1                                                                             Y    Z  n  M   R.sup.14                                                                              R.sup.15                                    __________________________________________________________________________     981  H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  O   CH.sub.3                                                                              4-Cl-phenyl                                 982  H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  O   Cyclopropyl                                                                           4-Cl-phenyl                                 983  H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  S   CH.sub.3                                                                              4-Cl-phenyl                                 984  H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  S   Cyclopropyl                                                                           4-Cl-phenyl                                 985  H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  S   SCH.sub.3                                                                             4-Cl-phenyl                                 986  H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  S   Phenyl 4-Cl-phenyl                                 987  H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  NH  Cyclopropyl                                                                           4-Cl-phenyl                                 988  H  OCH.sub.3                                                                           OCH.sub.3                                                                           O  1  S   CH.sub.3                                                                              4-Cl-phenyl                                 989  H  OCH.sub.3                                                                           OCH.sub.3                                                                           O  1  S   Cyclopropyl                                                                           4-Cl-phenyl                                 990  H  OCH.sub.3                                                                           OCH.sub.3                                                                           O  1  S   SCH.sub.3                                                                             4-Cl-phenyl                                 991  H  OCH.sub.3                                                                           SCH.sub.3                                                                           O  1  S   CH.sub.3                                                                              4-Cl-phenyl                                 992  H  OCH.sub.3                                                                           SCH.sub.3                                                                           O  1  S   Cyclopropyl                                                                           4-Cl-phenyl                                 993  H  OCH.sub.3                                                                           SCH.sub.3                                                                           O  1  S   SCH.sub.3                                                                             4-Cl-phenyl                                 994  H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  S   CH.sub.3                                                                              4-CH.sub.3 -phenyl                          995  H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  S   Cyclopropyl                                                                           4-CH.sub.3 -phenyl                          996  H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  S   SCH.sub.3                                                                             4-CH.sub.3 -phenyl                          997  H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  S   CH.sub.3                                                                              4-CF.sub.3 -phenyl                          998  H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  S   Cyclopropyl                                                                           4-CF.sub.3 -phenyl                          999  H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  S   SCH.sub.3                                                                             4-CF.sub.3 -phenyl                          1000 H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  S   CH.sub.3                                                                              4-OCH.sub.3 -phenyl                         1001 H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  S   Cyclopropyl                                                                           4-OCH.sub.3 -phenyl                         1002 H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  S   SCH.sub.3                                                                             4-OCH.sub.3 -phenyl                         1003 H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  S   CH.sub.3                                                                              CH.sub.3                                    1004 H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  S   Cyclopropyl                                                                           CH.sub.3                                    1005 H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  S   SCH.sub.3                                                                             CH.sub.3                                    1006 H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  S   CH.sub.3                                                                              C.sub.4 H.sub.9                             1007 H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  S   Cyclopropyl                                                                           C.sub.4 H.sub.9                             1008 H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  S   SCH.sub.3                                                                             C.sub.4 H.sub.9                             1009 H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  S   Cyclopropyl                                                                           4-OC.sub.2 H.sub.5 -phenyl                  1010 H  OCH.sub.3                                                                           NHCH.sub.3                                                                          O  1  S   Cyclopropyl                                                                           4-Phenoxyphenyl                             __________________________________________________________________________     Comp.                                                                          No.    X   R1   Y     Z  n   M   Q                                             __________________________________________________________________________     1011   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   C.sub.4 H.sub.9                               1012   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 Cl        1013   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   CH.sub.2 CH.sub.2 OC.sub.2 H.sub.5            1014   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   CH.sub.2 CH.sub.2 SC.sub.2 H.sub.5            1015   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   CH.sub.2 CH.sub.2 NHC.sub.2 H.sub.5           1016   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   Benzyl                                        1017   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   2-CH.sub.3 -benzyl                            1018   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   3-CH.sub.3 -benzyl                            1019   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   4-CH.sub.3 -benzyl                            1020   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   Phenetyl                                      1021   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   S   Benzyl                                        1022   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   NH  Benzyl                                        1023   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   3-Pyridylmethyl                               1024   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   CH.sub.2 CH═CH2                           1025   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   CH.sub.2 CH═CCl.sub.2                     1026   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   CH.sub.2 CH═CH-phenyl                     1027   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   CH.sub.2 C.tbd.CH                             1028   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   CH.sub.2 C.tbd.C--CH.sub.3                    1029   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   CH.sub.2 C.tbd.C-phenyl                       1030   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   Benzoyl                                       1031   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   4-Cl-benzoyl                                  1032   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   4-CH.sub.3 -benzoyl                           1033   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   4-CF.sub.3 -benzoyl                           1034   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   4-OCH.sub.3 -benzoyl                          1035   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   CO-benzyl                                     1036   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   S   CO-benzyl                                     1037   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   NH  CO-benzyl                                     1038   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   4-Toluenesulfonyl                             1039   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   O   Benzylsulfonyl                                1040   H   OCH.sub.3                                                                           NHCH.sub.3                                                                           O  1   NH  4-Toluenesulfonyl                             __________________________________________________________________________     Comp. No.  Physical data                                                       __________________________________________________________________________     474        84-87° C.                                                    475        105-106° C.                                                  476        117-118° C.                                                  477        2.23(3H, s), 3.39(3H, s), 3.71(3H, s), 5.24(1H, s), 5.27(1H,                   d, J=                                                                          12.2), 5.51(1H, d, J=12.2), 7.30-7.54(6H, m), 7.58(2H, m)           478        120-122° C.                                                  479        2.23(3H, s), 3.75(3H, s), 3.77(1H, d, J=5.5), 5.34(1H, d,                      J=12.2),                                                                       5.42(1H, d, J=12.2), 7.29-7.38(5H, m), 7.43-7.48(1H, m),                       7.56(2H,                                                                       d, J=8.6)                                                           480        2.84(3H, d, J=4.9), 3.34(3H, s), 5.13(1H, s), 5.23(1H, d,                      J=12.2),                                                                       5.65(1H, d, J=12.2), 6.80(1H, brs), 7.27-7.40(6H, m),                          7.41-7.48(1H,                                                                  m), 7.53-7.58(2H, m), 8.10(1H, s)                                   481        2.80(3H, d, J=4.9), 4.66(1H, brs), 5.25(1H, d, J=12.2),                        5.41(1H, d,                                                                    J=12.2), 5.42(1H, s), 6.60(1H, brs), 7.32-7.57(9H, m),                         8.06(1H, s)                                                         482        3.40(3H, s), 3.72(3H, s), 5.25(1H, s), 5.25(1H, d, J=12.2),                    5.50(1H,                                                                       d, J=12.2), 7.31-7.65(9H, m), 8.12(1H, s)                           483        3.74(1H, d, J=5.5), 3.75(3H, s), 5.31(1H, d, J=12.2), 5.42(1H,                 d,                                                                             J=12.2), 5.59(1H, d, J=5.5), 7.34-7.49(6H, m), 7.41-7.50(1H,                   m),                                                                            7.52-7.66(2H, m), 8.11(1H, s)                                       484        144-145° C.                                                  486        123-125° C.                                                  487        111.5-112.5° C.                                              488        2.26(3H, s), 3.39(3H, s), 3.71(3H, s), 5.27(1H, s), 5.28(1H,                   d, J=12.2),                                                                    5.52(1H, d, J=12.2), 7.32-7.40(5H, m), 7.43-7.56(2H, m),                       7.61-                                                                          7.69(2H, m)                                                         489        2.24(3H, s), 2.65(3H, d, J=4.9), 4.83(1H, brs), 5.23(1H, d,                    J=12.2),                                                                       5.43(1H, d, J=12.2), 5.45(1H, s), 6.59(1H, brs), 7.31-7.40(6H,                 m),                                                                            7.44-7.48(1H, m), 7.52-7.58(2H, m)                                  490        93-94° C.                                                    491        2.26(3H, s), 3.75(3H, S), 5.35(1H, d, J=12.2), 5.42(1H, d,                     J=12.2),                                                                       5.59(1H, s), 7.32-7.41(6H, m), 7.45-7.50(1H, m), 7.58-7.65(2H,                 m)                                                                  492        99-101.5° C.                                                 493        141.5-142.5° C.                                              494        74-74.5° C.                                                  495        2.21(3H, s), 2.68(3H, d, J=4.9), 3.82(3H, s), 4.95(1H, brs),                   5.20(1H,                                                                       d, J=12.2) 5.40(1H, d, J=12.2), 5.45(1H, s), 6.64(1H, brs),                    6.89(2H,                                                                       d, J=8.5), 7.31-7.48(4H, m), 7.50(2H, d, J=8.5)                     496        2.20(3H, s), 3.82(3H, s), 5.21(1H, d, J=12.2), 5.39(1H, brs),                  5.43                                                                           (1H, d, J=12.2), 5.48(1H, s), 6.79(1H, brs), 6.88(2H, d,                       J=8.5), 7.28-                                                                  7.46(4H, m), 7.49(2H, d, J=8.5)                                     497        72.5-73.5° C.                                                498        2.22(3H, s), 2.35(3H, s), 2.81(3H, d, J=5.5), 3.33(3H, s),                     5.15(1H, s)                                                                    5.26(1H, d, J=12.2), 5.63(1H, d, J=12.2), 6.77(1H, brs),                       7.15(2H, d,                                                                    J=7.9), 7.28-7.48(4H, m), 7.52(2H, d, J=7.9)                        499        122-123° C.                                                  500        2.23(3H, s), 2.36(3H, s), 3.39(3H, s), 3.71(3H, s), 5.26(1H,                   d, J=                                                                          12.2), 5.27(1H, s), 5.38(1H, d, J=12.2), 7.16(2H, d, J=7.9),                   7.32-                                                                          7.51(4H, m), 7.54(2H, d, J=7.9)                                     501        2.22(3H, s), 2.35(3H, s), 2.66(3H, d, J=4.9), 4.91(1H, brs),                   5.21                                                                           (1H, d, J=12.2), 5.41(1H, d, J=12.2), 5.45(1H, s), 6.62(1H,                    brs),                                                                          7.17(2H, d, J=7.9), 7.31-7.47(6H, m)                                502        105-106° C.                                                  504        2.22(3H, s), 2.83(3H, d, J=4.9), 3.32(3H, s), 5.11(1H, s),                     5.26(1H,                                                                       d, J=12.2), 5.63(1H, d, J=12.2), 6.78(1H, brs), 7.23-7.46(7H,                  m)                                                                  505        118-120.5° C.                                                506        2.22(3H, s), 3.38(3H, s), 3.71(3H, s), 5.22(1H, s), 5.26(1H,                   d, J=                                                                          12.2), 5.50(1H, d, J=12.2), 7.24-7.65(7H, m)                        507        2.21(3H, s), 2.66(3H, d, J=4.9), 5.23(1H, d, J=12.2), 5.30(1H,                 d, J=                                                                          12.2), 5.39(1H, s), 6.55(1H, brs), 7.15-7.47(7H, m)                 510        2.23(3H, s), 2.56(3H, d, J=4.9), 4.72(1H, d, J=3.1), 5.22(1H,                  d, J=                                                                          12.2), 5.41(1H, s), 5.42(1H, d, J=12.2), 6.58-6.68(1H, m),                     7.19-7.49                                                                      (8H, m)                                                             513        2.24(3H, s), 2.81(3H, d, J=4.9), 3.32(3H, s), 5.12(1H, s),                     5.28(1H,                                                                       d, J=12.2), 5.62(1H, d, J=12.2), 6.78(1H, brs), 7.21-7.48(8H,                  m)                                                                  515        2.25(3H, s), 3.39(3H, s), 3.71(3H, s), 5.24(1H, s), 5.27(1H,                   d, J=                                                                          12.8), 5.51(1H, d, J=12.2), 7.22-7.65(8H, m)                        516        2.22(3H, s), 2.72(3H, d, J=4.9), 4.62(1H, brs), 5.26(1H, d,                    J=12.2),                                                                       5.43(1H, s), 6.48(1H, brs), 7.27-7.65(8H, m)                        517        87-88° C.                                                    518        2.23(3H, s), 3.40(3H, s), 3.72(3H, s), 5.24(1H, s), 5.28(1H,                   d, J=                                                                          12.2), 5.52(1H, d, J=12.2), 7.25-7.66(8H, m)                        520        2.21(3H, s), 2.80(3H, d, J=4.9), 3.31(3H, s), 5.09(1H, s),                     5.25(1H, d,                                                                    J=12.2), 5.59(1H, d, J=12.2), 6.76(1H, brs), 7.29-7.57(7H,                     m),                                                                            7.67(1H, d, J=7.3)                                                  523        2.27(3H, s), 2.83(3H, d, J=4.9), 3.33(3H, s), 5.13(1H, s),                     5.29(1H, d,                                                                    J=12.2), 5.70(1H, d, J=12.2), 6.78(1H, brs), 7.29-7.50(5H,                     m),                                                                            7.60(1H, d, J=7.9), 7.82(1H, d, J=7.9), 7.89(1H, s)                 526        2.26(3H, s), 2.84(3H, d, J=4.9), 3.33(3H, s), 5.12(1H, s),                     5.29(1H, d,                                                                    J=12.2), 5.70(1H, d, J=12.2), 6.80(1H, brs), 7.29-7.48(4H,                     m),                                                                            7.60(2H, d, J=7.9), 7.75(2H, d, J=7.9)                              527        2.27(3H, s), 3.40(3H, s), 3.72(3H, s), 5.24(1H, s), 5.30(1H,                   d, J=                                                                          12.2), 5.54(1H, d, J=12.2), 7.32-7.57(4H, m), 7.61(2H, d,                      J=8.5),                                                                        7.76(2H, d, J=8.5)                                                  529        2.28(3H, s), 2.84(3H, d, J=4.9), 3.33(3H, s), 5.11(1H, s),                     5.32(1H, d,                                                                    J=12.8), 5.74(1H, d, J=12.8), 6.84(1H, brs), 7.29-7.41(3H, m),                 7.42-                                                                          7.47(1H, m), 7.80(2H, d, J=8.6), 8.18(2H, d, J=8.6)                 532        2.19(3H, s), 2.26(3H, s), 2.76(3H, d, J=4.9), 3.31(3H, s),                     5.13(1H, s),                                                                   5.26(1H, d, J=12.2), 5.57(1H, d, J=12.2), 6.75(1H, brs),                       7.10-                                                                          7.28(4H, m), 7.29-7.38(3H, m), 7.42-7.47(1H, m)                     535        2.23((3H, s), 2.36(3H, s), 2.82(3FH, d, J=4.9), 3.32(3H, s),                   5.14(1H,                                                                       s), 5.27(1H, d, J=12.2), 5.63(1H, d, J=12.2), 6.76(1H, brs),                   7.10-                                                                          7.45(8H, m)                                                         541        1.10(3H, t, J=7.3), 2.74(2H, q, J=7.3), 2.83(3H, d, J=4.9),                    3.32(3H,                                                                       s), 5.12(1H, s), 5.25(1H, d, J=12.2), 5.65(1H, d, J=12.2),                     6.78(1H,                                                                       brs), 7.32(2H, d, J=8.5), 7.35-7.53(4H, m), 7.56(2H, d,                        J=8.5)                                                              542        1.11(3H, t, J=7.9), 2.75(2H, q, J=7.9), 3.39(3H, s), 3.71(3H,                  s),                                                                            5.24(1H, s), 5.25(1H, d, J=12.2), 5.50(1H, d, J=12.2),                         7.33(2H, d,                                                                    J=8.5), 7.36-7.65(4H, m), 7.57(2H, d, J=8.5)                        544        1.10(3H, t, J=7.6), 2.73(2H, q, J=7.6), 3.32(3H, s), 3.81(3H,                  s), 5.14                                                                       (1H, s), 5.24(1H, d, J=12.2), 5.61(1H, d, J=12.2), 6.75(1H,                    brs),                                                                          6.84(2H, d, J=8.6), 7.30-7.40(3H, m), 7.45-7.50(1H, m),                        7.56(2H, d,                                                                    J=8.6)                                                              547        1.86(6H, s), 2.82(3H, d, J=4.9), 3.33(3H, s), 5.09(1H, s),                     5.11(1H, d                                                                     J=12.2), 5.43(1H, d, J=12.2), 6.72(1H, brs), 7.30-7.40(4H, m)       548        1.87(6H, s), 3.38(3H, s), 3.70(3H, s), 5.08(1H, d, J=12.2),                    5.22(1H,                                                                       s), 5.32(1H, d, J=12.2), 7.31-7.39(3H, m), 7.46-7.48(1H, m)         550        0.89(3H, t, J=7.3), 1.23-1.35(2H, m), 1.40-1.50(2H, m),                        1.83(3H, s),                                                                   2.14 & 2.35(2H in total, each t, J=7.3), 2.83(3H, d, J=4.9),                   3.33(3H, s), 5.08(1H, s), 5.09 & 5.11(1H in total, each d,                     J=12.2),                                                                       5.42 & 5.43(1H in total, each d, J=12.2), 6.80(1H, brs),                       7.31-7.39(4H,                                                                  m).                                                                 551        0.87-0.92(3H, m), 1.25-1.40(2H, m), 1.45-1.55(2H, m), 1.85 &                   1.86                                                                           (3H in total, each s), 2.16 & 2.35(2H in total, each t,                        J=7.3), 3.37(3H,                                                               s), 3.70(3H, s), 5.07 & 5.10(1H in total, each d, J=12.2),                     5.21(1H, s),                                                                   5.33 & 5.34(1H in total, each d, J=12.2), 7.31-7.39(3H, m),                    7.42-                                                                          7.44(1H, m)                                                         553        2.19(3H, s), 2.78(3H, d, J=4.9), 3.32(3H, s), 3.80(3H, s),                     5.14(1H, s)                                                                    5.25(1H, d, J=12.2), 5.57(1H, d, J=12.2), 6.76(1H, brs),                       6.87-6.95                                                                      (2H, m), 7.25-7.40(5H, m), 7.45-7.50(1H, m)                         556        2.23(3H, s), 2.82(3H, d, J=4.9), 3.32(3H, s), 3.82(3H, s),                     5.13(1H, s)                                                                    5.27(1H, d, J=12.2), 5.65(1H, d, J=12.2), 6.85(1H, brs),                       6.90-6.92                                                                      (1H, m), 7.20-7.26(3H, m), 7.30-7.45(3H, m), 7.48-7.52(1H, m)       559        2.22(3H, s), 2.26(3H, s), 2.27(3H, s), 2.81(3H, d, J=4.9),                     3.33(3H, s)                                                                    5.14(1H, s), 5.27(1H, d, J=12.2), 5.63(1H, d, J=12.2),                         6.74-6.75(1H,                                                                  m), 7.10(1H, d, J=7.9), 7.28-7.49(6H, m)                            562        2.21(3H, s), 2.84(3H, d, J=4.9), 3.33(3H, s), 5.11(1H, s),                     5.27(1H, d,                                                                    J=12.2), 5.68(1H, d, J=12.2), 6.78-6.79(1H, m), 7.28-7.49(6H,                  m),                                                                            7.73(1H, brs)                                                       571        1.93(3H, s), 2.35(3H, s), 2.85(3H, d, J=4.9), 3.32(3H, s),                     5.50(1H, s),                                                                   5.30(1H, d, J=12.2), 5.79(1H, d, J=12.2), 6.82(1H, brs),                       7.29-                                                                          7.43(4H, m)                                                         572        1.94(3H, s), 2.36(3H, s), 3.39(3H, s), 3.72(3H, s), 5.15(1H,                   s), 5.34                                                                       (1H, d, J=12.2), 5.56(1H, d, J=12.2), 7.33-7.65(4H, m)              575        2.16(3H, s), 3.33(3H, s), 3.67(3H, s), 5.15(1H, s), 5.31(1H,                   d, J=                                                                          12.2), 5.55(1H, d, J=12.2), 7.33-7.55(7H, m), 7.79-7.83(2H,                    m)                                                                  577        2.28(3H, s), 2.83(3H, d, J=4.9), 3.34(3H, s), 5.16(1H, s),                     5.30(1H, d                                                                     J=12.2), 5.68(1H, d, J=12.2), 6.77(1H, brs), 7.31(7H, m),                      7.57-7.62                                                                      (4H, m), 7.71(2H, d, J=8.5)                                         580        2.38(3H, s), 2.75(3H, d, J=4.9), 3.30(3H, S0, 5.18(1H, s),                     5.34(1H,                                                                       d, J=12.2), 5.68(1H, d, J=12.2), 6.75(1H, brs), 7.33-7.55(8H,                  m),                                                                            7.81-7.93(3H, m)                                                    581        2.38(3H, s), 3.39(3H, s), 3.69(3H, s), 5.31(1H, s), 5.32(1H,                   d, J=                                                                          12.2), 5.56(1H, d, J=12.2), 7.36-7.60(8H, m), 7.83-7.95(3H,                    m)                                                                  583        2.17(3H, s), 2.83(3H, d, J=4.9), 3.34(3H, s), 5.10(1H, s),                     5.29(1H,                                                                       d, J=12.2), 5.62(1H, d, J=12.2), 6.43(1H, dd, J=3.7, 1.8),                     6.62(1H, d,                                                                    J=3.7), 6.79(1H, brs), 7.28-7.47(5H, m)                             584        2.18(3H, s), 3.40(3H, s), 3.71(3H, s), 5.23(1H, s), 5.28(1H,                   d, J=                                                                          12.2), 5.52(1H, d, J=12.2), 6.44(1H, dd, J=3.7, 1.8), 6.64(1H,                 d, J=                                                                          3.7), 7.32-7.55(5H, m)                                              586        2.25(3H, s), 2.84(3H, d, J=4.9), 3.35(3H, s), 5.13(1H, s),                     5.23(1H,                                                                       d, J=12.2), 5.62(1H, d, J=12.2), 6.79(1H, brs), 6.99(1H, dd,                   J=4.9,                                                                         3.7), 6.98-7.47(6H, m)                                              587        2.26(3H, s), 3.40(3H, s), 3.71(3H, s), 5.24(1H, d, J=12.2),                    5.25(1H,                                                                       s), 5.47(1H, d, J=12.2), 7.00(1H, dd, J=5.5, 3.7),                             7.21-7.53(6H, m)                                                    589        2.35(3H, s), 2.84(3H, d, J=5.5), 3.33(3H, s), 5.14(1H, s),                     5.30(1H,                                                                       d, J=12.2), 5.73(1H, d, J=12.2), 6.80(1H, brs), 7.21-7.49(5H,                  m),                                                                            7.65(1H, dt, J=1.8, 7.9), 7.90(1H, d, J=7.9), 8.56-8.59(1H,                    m)                                                                  590        2.36(3H, s), 3.40(3H, s), 3.71(3H, s), 5.25(1H, s), 5.31(1H,                   d, J=                                                                          12.2), 5.55(1H, d, J=12.2), 7.22-7.56(5H, m), 7.65(1H, dt,                     J=1.8,                                                                         7.9), 7.89(1H, d, J=7.9), 8.59(1H, dd, J=4.9, 1.8)                  592        81-83° C.                                                    593        2.33(3H, s), 3.41(3H, s), 3.73(3H, s), 5.24(1H, s), 5.35(1H,                   d, J=                                                                          12.2), 5.58(1H, d, J=12.2), 7.32-7.56(4H, m), 8.49-8.53(2H,                    m), 9.15                                                                       (1H, d, J=1.2)                                                      603        2.23(3H, s), 3.25(3H, d, J=4.9), 3.33(3H, s), 5.29(1H, d,                      J=12.2),                                                                       5.51(1H, s), 5.80(1H, d, J=12.2), 7.25-7.36(5H, m),                            7.42-7.47(1H,                                                                  m), 7.58(2H, d, J=9.2), 8.77(1H, s)                                 606        105-107° C.                                                  609        94.5-95.5° C.                                                610        2.27(3H, s), 3.26(3H, d, J=4.9), 3.33(3H, s), 5.32(1H, d,                      J=12.2),                                                                       5.51(1H, s), 5.84(1H, d, J=12.2), 7.27-7.48(4H, m), 7.60(2H,                   d, J=                                                                          7.9), 7.75(2H, d, J=7.9)                                            616        1.10(3H, t, J=7.6), 2.34(3H, s), 2.76(2H, q, J=7.6), 2.81(3H,                  d, J=                                                                          4.9), 3.32(3H, s), 5.14(1H, s), 5.26(1H, d, J=12.2), 5.63(1H,                  d, J=                                                                          12.2), 6.76(1H, brs), 7.14(2H, d, J=7.8), 7.30-7.40(3H, m),                    7.45-                                                                          7.50(1H, m), 7.51(2H, d, J=7.8)                                     627        1.55-1.68(6H, m), 2.19(2H, t, J=6.1), 2.44-2.49(2H, m),                        2.83(3H, d,                                                                    J=4.9), 3.33(3H, s), 5.09(1H, s), 5.10(1H, d, J=12.2),                         5.42(1H, d,                                                                    J=12.2), 6.75(1H, brs), 7.28-7.42(4H, m)                            628        1.55-1.69(6H, m), 2.08(2H, t, d=6.1), 2.40-2.52(2H, m),                        3.38(3H, s),                                                                   3.70(3H, s), 5.07(1H, d, J=12.2), 5.22(1H, s), 5.33(1H, d,                     J=12.2),                                                                       7.28-7.62(4H, m)                                                    629        137.5-138.5° C.                                              630        2.88-2.93(2H, m), 3.01-3.05(2H, m), 3.41(3H, s), 3.72(3H, s),                  5.26                                                                           (1H, d, J=12.2), 5.30(1H, s), 5.49(1H, d, J=12.2),                             7.24-7.37(5H, m),                                                              7.45-7.54(2H, m), 7.69(2H, d, J=7.3)                                631        1.20(3H, t, J=7.3), 2.23(3H, s), 3.39(3H, s), 4.14-4.22(2H,                    m), 5.22                                                                       (1H, s), 5.27(1H, d, J=12.2), 5.52(1H, d, J=12.2),                             7.30-7.40(4H, m),                                                              7.41-7.43(1H, m), 7.51-7.56(1H, m), 7.58(2H, d, J=8.6)              632        1.16(3H, t, J=7.3), 2.22(3H, s), 3.28-3.32(2H, m), 3.32(3H,                    s), 5.10                                                                       (1H, s), 5.25(1H, d, J=12.2), 5.66(1H, d, J=12.2), 6.72(1H,                    brs),                                                                          7.29-7.38(5H, m), 7.43-7.46(1H, m), 7.58(2H, d, J=8.6)              633        1.22-1.28(3H, m), 2.22(3H, s), 3.45-3.65(2H, m), 3.70(3H, s),                  5.27                                                                           (1H, d, J=12.2), 5.32(1H, s), 5.50(1H, d, J=12.2),                             7.29-7.38(4H, m),                                                              7.41-7.43(1H, m), 7.53-7.55(1H, m), 7.57(2H, d, J=8.6)              634        1.23(3H, t, J=7.3), 2.21(3H, s), 2.83(3H, d, J=4.9), 3.45(2H,                  q, J=                                                                          7.3), 5.21(1H, s), 5.25(1H, d, J=12.2), 5.67(1H, d, J=12.2),                   6.80(1H,                                                                       brs), 7.29-7.32(4H, m), 7.37-7.42(2H, m), 7.57(2H, d, J=8.6)        635        0.87(3H, t, J=7.3), 1.29-1.35(2H, m), 1.53-1.58(2H, m),                        2.21(3H, s),                                                                   2.83(3H, d, J=4.9), 3.40(2H, t, J=7.3), 5.19(1H, s), 5.25(1H,                  d, J=                                                                          12.2), 5.68(1H, d, J=12.2), 6.80(1H, brs), 7.29-7.43(6H, m),                   7.57                                                                           (2H, d, J=8.6)                                                      636        0.87(3H, t, J=7.3), 1.23-1.45(2H, m), 1.56-1.63(2H, m),                        2.22(3H, s),                                                                   3.39-3.58(2H, m), 3.69(3H, s), 5.27(1H, d, J=12.2), 5.30(1H,                   s),                                                                            5.49(1H, d, J=12.2), 7.29-7.39(4H, m), 7.41-7.43(1H, m),                       7.52-7.59                                                                      (3H, m)                                                             637        102-103° C.                                                  638        2.20(3H, s), 2.83(3H, s), 3.00(3H, s), 3.46(3H, s), 5.25(1H,                   d, J=                                                                          12.2), 5.38(1H, s), 5.45(1H, d, J=12.2), 7.30-7.35(5H, m),                     7.44-7.47                                                                      (1H, m), 7.58(2H, d, J=8.6)                                         639        2.15(3H, s), 2.22(3H, s), 2.62(3H, d, J=4.9), 5.33(1H, d,                      J=12.2),                                                                       5.52(1H, d, J=12.2), 6.22(1H, brs), 6.47(1H, s), 7.31(2H, d,                   J=8.6),                                                                        7.34-7.39(2H, m), 7.42-7.53(2H, m), 7.56(2H, d, J=8.6)              671        1.06(3H, t, J=7.3), 1.84(3H, s), 2.16 & 2.35(2H in total, each                 q,                                                                             J=7.3), 2.82(3H, d, J=4.9), 3.33(3H, s), 5.09 & 5.11(1H in                     total, each                                                                    d, J=12.2), 5.11(1H, s), 5.40 & 5.42(1H in total, each d,                      J=12.2),                                                                       6.80(1H, brs), 7.30-7.39(4H, m)                                     672        1.04-1.10(3H, m), 1.84 & 1.85(3H in total, each s), 2.16 &                     2.34(2H in                                                                     total, each q, J=7.3), 3.38(3H, s), 3.70(3H, s), 5.07 &                        5.12(1H in total,                                                              each d, J=12.2), 5.27(1H, s), 5.34 & 5.36(1H in total, each d,                 J=12.2),                                                                       7.30-7.38(3H, m), 7.42-7.45(1H, m)                                  678        2.20(3H, s), 2.83(3H, d, J=4.9), 3.33(3H, s), 3.91(3H, s),                     5.13(1H, s),                                                                   5.25(1H, d, J=12.2), 5.65(1H, d, J=12.2), 6.77(1H, brs),                       6.89(1H,                                                                       d, J=8.5), 7.29-7.46(4H, m), 7.50(1H, dd, J=8.5, 2.4),                         7.69(1H, d, J=                                                                 2.4)                                                                680        2.21(3H, s), 2.38(3H, s), 2.83(3H, d, J=4.9), 3.33(3H, s),                     5.12(1H, s)                                                                    5.27(1H, d, J=12.2), 5.65(1H, d, J=12.2), 6.78(1H, brs),                       7.29-7.51                                                                      (7H, m)                                                             682        2.23(3H, s), 2.81(3H, d, J=4.9), 3.32(3H, s), 5.12(1H, s),                     5.27(1H, d,                                                                    J=12.2), 5.66(1H, d, J=12.2), 6.51(1H, t, J=73.8), 6.81(1H,                    brs),                                                                          7.08(2H, d, J=8.6), 7.30-7.39(3H, m), 7.42-7.47(1H, m),                        7.63(2H, d,                                                                    J=8.6)                                                              684        2.22(3H, s), 2.82(3H, d, J=4.9), 3.33(3H, s), 3.89(3H, s),                     3.91(3H, s),                                                                   5.14(1H, s), 5.26(1H, d, J=12.2), 5.65(1H, d, J=12.2),                         6.76-6.78(1H,                                                                  m), 6.83(1H, d, J=8.5), 7.13(1H, dd, J=8.5, 2.4), 7.29(1H, d,                  J=2.4), 7.29-7.49(4H, m)                                            686        2.18(3H, s), 2.23(3H, s), 2.30(3H, s), 2.78(3H, d, J=4.9),                     3.32(3H, s), 5.13(1H, s), 5.25(1H, d, J=12.2), 5.58(1H, d,                     J=12.2),                                                                       6.75(1H, brs), 6.97-7.47(7H, m)                                     688        2.22(3H, s), 2.78(3H, d, J=4.9), 3.31(3H, s), 5.14(1H, s),                     5.27(1H, d,                                                                    J=12.2), 5.66(1H, d, J=12.2), 6.80(1H, brs), 6.93-7.01(4H,                     m),                                                                            7.10(1H, t, J=7.3), 7.28-7.39(5H, m), 7.41-7.67(1H, m),                        7.60(2H, d,                                                                    J=9.2)                                                              690        2.23(3H, d, J=3.1), 2.81(3H, d, J=4.9), 3.33(3H, s), 3.80(3H,                  s),                                                                            5.13(1H, s), 5.25(1H, d, J=12.2), 5.62(1H, d, J=12.2),                         6.60(1H, dd,                                                                   J=12.8, 2.4), 6.66(1H, dd, J=8.5, 2.4), 7.29-7.47(5H, m)            692        2.20(3H, s), 2.83(3H, d, J=4.9), 3.33(3H, s), 3.90(3H, s),                     5.13(1H, s), 5.25(1H, d, J=12.2), 5.64(1H, d, J=12.2),                         6.77-6.79(1H,                                                                  m), 6.92(1H, t, J=8.5), 7.29-7.49(6H, m)                            698        2.21(3H, s), 2.82(3H, d, J=4.9), 3.32(3H, s), 5.12(1H, s),                     5.26(1H, d,                                                                    J=12.2), 5.66(1H, d, J=12.2), 6.75(1H, brs), 7.28-7.40(3H, m),                 7.42-                                                                          7.55(5H, m)                                                         701        2.22(3H, s), 2.82(3H, d, J=4.9), 3.32(3H, s), 5.13(1H, s),                     5.25(1H, d,                                                                    J=12.2), 5.65(1H, d, J=12.2), 6.73(1H, brs), 7.00-7.05(2H, m),                 7.27-                                                                          7.36(3H, m), 7.43-6.45(1H, m), 7.58-7.62(2H, m)                     702        1.41(3H, t, J=7.3), 2.21(3H, s), 2.81)(3H, d, J=4.9), 3.33(3H,                 s),                                                                            4.05(2H, q, J=7.3), 5.15(1H, s), 5.25(1H, d, J=12.2), 5.62(1H,                 d, J=                                                                          12.2), 6.75(1H, brs), 6.86(2H, d, J=8.5), 7.30-7.48(4H, m),                    7.56(2H,                                                                       d, J=8.5)                                                           704        0.97(3H, t, J=7.3), 1.49(2H, sextet, J=7.3), 1.77(2H, quintet,                 J=7.3),                                                                        2.21(3H, s), 2.81(3H, d, J=4.9), 3.33(3H, s), 3.97(2H, t,                      J=7.3),                                                                        5.15(1H, s), 5.25(1H, d, J=12.2), 5.62(1H, d, J=12.2),                         6.75(1H, brs),                                                                 6.86(2H, d, J=8.5), 7.28-7.48(4H, m), 7.56(2H, d, J=8.5)            707        1.31(9H, s), 2.23(3H, s), 2.80(3H, d, J=4.9), 3.32(3H, s),                     5.14(1H,                                                                       s), 5.26(1H, d, J=12.2), 5.63(1H, d, J=12.2), 6.75(1H, brs),                   7.30-                                                                          7.38(5H, m), 7.42-7.47(1H, m), 7.56(2H, d, J=8.6)                   710        1.22(3H, t, J=7.6), 2.22(3H, s), 2.65(2H, q, J=7.6), 2.81(3H,                  d, J=                                                                          4.9), 3.32(3H, s), 5.14(1H, s), 5.26(1H, d, J=12.2), 5.63(1H,                  d, J=                                                                          12.2), 6.75(1H, brs), 7.17(2H, d, J=8.6), 7.30-7.38(3H, m),                    7.44-7.47                                                                      (1H, m), 7.54(2H, d, J=8.6)                                         717        1.15(3H, t, J=7.3), 2.22(3H, s), 2.34(3H, s), 3.21-3.40(2H,                    m), 3.32                                                                       (3H, s), 5.13(1H, s), 5.26(1H, d, J=12.2), 5.65(1H, d,                         J=12.2), 6.77                                                                  (1H, brs), 7.14(2H, d, J=8.5), 7.28-7.39(3H, m), 7.44-7.48(1H,                 m),                                                                            7.52(2H, d, J=8.5)                                                  718        1.19(3H, t, J=7.0), 2.21(3H, s), 2.34(3H, s), 2.82(3H, d,                      J=4.9), 3.47                                                                   (2H, q, J=7.0), 5.23(1H, s), 5.26(1H, d, J=12.2), 5.67(1H, d,                  J=12.2),                                                                       6.85(1H, brs), 7.20-7.53(8H, m)                                     721        1.15(3H, t, J=7.3), 2.22(3H, s), 2.34(3H, s), 3.22-3.36(2H,                    m), 3.32                                                                       (3H, s), 3.81(3H, s), 5.13(1H, s), 5.25(1H, d, J=12.2),                        5.63(1H, d,                                                                    J=12.2), 6.76(1H, brs), 6.86(2H, d, J=9.2), 7.29-7.38(3H, m),                  7.43-                                                                          7.48(1H, m), 7.58(2H, d, J=9.2)                                     722        1.18(3H, t, J=7.0), 2.20(3H, s), 2.82(3H, d, J=4.9), 3.48(2H,                  q, J=                                                                          7.0), 3.81(3H, s), 5.23(1H, s), 5.25(1H, d, J=12.2), 5.64(1H,                  d,                                                                             J=12.2), 6.80(1H, brs), 6.87(2H, d, J=8.3), 7.29-7.46(4H, m),                  7.58(2H,                                                                       d, J=8.3)                                                           725        1.16(3H, t, J=7.3), 2.26(3H, s), 3.24-3.37(2H, m), 3.33(3H,                    s),                                                                            5.11(1H, s), 5.29(1H, d, J=12.2), 5.71(1H, d, J=12.2),                         6.78(1H, brs),                                                                 7.29-7.40(3H, m), 7.44-7.47(1H, m), 7.59(2H, d, J=8.5),                        7.75(2H, d,                                                                    J=8.5)                                                              726        88˜90° C.                                              733        0.93(3H, t, J=7.3), 1.54(2H, sextet, J=7.3), 2.72(2H, t,                       J=7.3), 3.39                                                                   (3H, s), 3.71(3H, s), 5.24(1H, s), 5.25(1H, d, J=12.2),                        5.49(1H, d,                                                                    J=12.2), 7.29-7.53(4H, m), 7.32(2H, d, J=8.5), 7.56(2H, d,                     J=8.5)                                                              734        2.34(3H, s), 3.34(3H, s), 3.67(3H, s), 5.29(1H, s), 5.30(1H,                   d, J=                                                                          12.2), 5.58(1H, d, J=12.2), 7.70(1H, dd, J=5.5, 3.7),                          7.32-7.56(6H,                                                                  m)                                                                  735        2.32(3H, s), 2.79(3H, d, J=4.9), 3.29(3H, s), 5.18(1H, s),                     5.31(1H, d,                                                                    J=12.2), 5.72(1H, d, J=12.2), 6.74(1H, brs), 7.05-7.08(1H,                     m),                                                                            7.27-7.52(6H, m)                                                    736        0.92(3H, t, J=7.3), 1.53(2H, sextet, J=7.3), 2.71(2H, t,                       J=7.3), 2.83                                                                   (3H, d, J=4.9), 3.32(3H, s), 5.12(1H, s), 5.25(1H, d, J=12.2),                 5.65                                                                           (1H, d, J=12.2), 6.75-6.78(1H, m), 7.28-7.53(4H, m), 7.31(2H,                  d,                                                                             J=8.5), 7.55(2H, d, J=8.5)                                          737        3.29(3H, s), 3.39(3H, s), 3.71(3H, s), 4.62(2H, s), 5.22(1H,                   s), 5.28                                                                       (1H, d, J=12.2), 5.53(1H, d, J=12,2), 7.30-7.36(5H, m),                        7.39-7.44                                                                      (1H, m), 7.45-7.50(1H, m), 7.62-7.67(2H, m)                         738        2.81(3H, d, J=4.9), 3.29(3H, s), 3.32(3H, s), 4.62(2H, s),                     5.11(1H,                                                                       s), 5.27(1H, d, J=12.2), 5.57(1H, d, J=12.2), 6.78(1H, brs),                   7.30-                                                                          7.45(6H, m), 7.56-7.59(1H, m), 7.65-7.67(2H, m)                     739        1.10(3H, t, J=7.3), 1.16(3H, t, J=7.3), 2.74(2H, q, J=7.3),                    3.22-3.35                                                                      (2H, m), 3.32(3H, s), 5.10(1H, s), 5.26(1H, d, J=12.2),                        5.66(1H, d,                                                                    J=12.2), 6.78(1H, brs), 7.27-7.39(3H, m), 7.31(2H, d, J=8.6),                  7.42-                                                                          7.47(1H, m), 7.56(2H, d, J=8.6)                                     740        1.11(3H, t, J=7.3), 2.76(2H, q, J=7.3), 2.82(3H, d, J=4.9),                    3.32(3H,                                                                       s), 5.12(1H, s), 5.25(1H, d, J=12.8), 5.65(1H, d, J=12.8),                     6.51(1H, t,                                                                    J=73.9), 6.77(1H, brs), 7.09(2H, d, J=8.6), 7.28-7.39(3H, m),                  7.40-                                                                          7.48(1H, m), 7.63(2H, d, J=8.6)                                     741        2.51-2.89(7H, m), 3.31 & 3.35(3H in total, each s), 3.50 &                     3.79(2H                                                                        in total, each s), 5.08-5.20(2H, m), 5.44-5.55(1H, m),                         6.75(1H, brs),                                                                 7.09-7.20(4H, m), 7.25-7.45(4H, m)                                  756        0.89(3H, t, J=7.3), 1.56-1.63(2H, m), 2.21(3H, s), 2.84(3H, d,                 J=4.9),                                                                        3.36(2H, t, J=7.3), 5.20(1H, s), 5.25(1H, d, J=12.2), 5.69(1H,                 d, J=                                                                          12.2), 6.85(1H, brs), 7.29-7.44(6H, m), 7.58(2H, dd, J=8.6,                    1.8)                                                                757        0.88(3H, t, J=7.3), 1.56-1.63(2H, m), 2.21(3H, s), 2.34(3H,                    s), 2.83                                                                       (3H, d, J=4.9), 3.37(2H, t, J=7.3), 5.22(1H, s), 5.24(1H, d,                   J=12,2),                                                                       5.67(1H, d, J=12.2), 6.80(1H, brs), 7.14(2H, d, J=8.0),                        7.29-7.43(4H,                                                                  m), 7.52(2H, d, J=8.0)                                              758        0.88(3H, t, J=7.3), 1.56-1.64(2H, m), 2.21(3H, s), 2.83(3H, d,                 J=4.9),                                                                        3.37(2H, t, J=7.3), 3.8(3H, s), 5.22(1H, s), 5.24(1H, d,                       J=12.2),                                                                       5.67(1H, d, J=12.2), 6.80(1H, brs), 6.86(2H, d, J=8.3),                        7.29-7.46(4H,                                                                  m), 7.56(2H, d, J=8.3)                                              759        0.88(3H, t, J=7.3), 1.56-1.63(2H, m), 2.25(3H, s), 2.84(3H, d,                 J=4.9),                                                                        3.36(2H, t, J=7.3), 5.20(1H, s), 5.28(1H, d, J=12.2), 5.73(1H,                 d,                                                                             J=12.2), 6.85(1H, brs), 7.29-7.46(4H, m), 7.59(2H, d, J=8.0),                  7.73(2H,                                                                       d, J=8.0)                                                           773        2.18(3H, s), 2.21(3H, s), 2.30(3H, s), 2.78(3H, d, J=4.9),                     3.32(3H, s),                                                                   5.13(1H, s), 5.26(1H, d, J=12.2), 5.58(1H, d, J=12.2),                         6.76(1H, brs),                                                                 7.00-7.08(3H, m), 7.30-7.48(4H, m)                                  777        2.22(3H, s), 2.32(6H, s), 2.81(3H, d, J=4.9), 3.33(3H, s),                     5.14(1H, s)                                                                    5.28(1H, d, J=12.2), 5.64(1H, d, J=12.2), 6.77(1H, brs),                       6.99(1H, s),                                                                   7.24-7.48(6H, m)                                                    781        2.21(3H, s), 2.22(3H, s), 2.81(3H, d, J=4.9), 3.33(3H, s),                     3.83(3H, s)                                                                    5.14(1H, s), 5.26(1H, d, J=12.2), 5.62(1H, d, J=12.2),                         6.75(1H, brs),                                                                 6.79(1H, d, J=8.5), 7.28-7.49(6H, m)                                785        2.35(3H, s), 2.80(3H, d, J=4.9), 3.33(3H, s), 5.17(1H, s),                     5.33(1H, d,                                                                    J=12.2), 5.73(1H, d, J=12.2), 6.79(1H, brs), 7.29-7.40(3H, m),                 7.43-                                                                          7.51(3H, m), 7.78-7.86(3H, m), 7.91(1H, dd, J=8.8, 1.8),                       7.97(1H, s)                                                         813        2.05(3H, s), 2.81(3H, d, J=4.9), 3.34(3H, s), 5.15(1H, s),                     5.30(1H, d,                                                                    J=12.2), 5.68(1H, s, J=12.2), 6.75(1H, brs), 7.30-7.47(8H, m)       819        2.02(3H, s), 2.37(3H, s), 2.78(3H, d, J=4.9), 3.35(3H, s),                     5.16(1H, s)                                                                    5.30(1H, d, J=12.2), 5.63(1H, d, J=12.2), 6.73(1H, brs),                       7.18-7.58(8H,                                                                  m)                                                                  824        2.06(3H, s), 2.82(3H, d, J=4.9), 3.34(3H, s), 5.15(1H, s),                     5.31(1H, d,                                                                    J=12.2), 5.71(1H, d, J=12.2), 6.75(1H, brs), 7.29-7.47(4H, m),                 7.54                                                                           (2H, d, J=7.9), 7.67(2H, d, J=7.9)                                  837        2.05(3H, s), 2.78(3H, d, J=4.9), 3.35(3H, s), 3.82(3H, s),                     5.16(1H, s),                                                                   5.30(1H, d, J=12.2), 5.63(1H, d, J=12.2), 6.73(1H, brs),                       6.92(2H, d,                                                                    J=8.6), 7.27-7.48(6H, m)                                            873        2.12(3H, s), 2.32(3H, s), 2.81(3H, d, J=4.9), 3.36(3H, s),                     .511(1H, s),                                                                   5.17(1H, d, J=12.2), 5.51(1H, d, J=12.2), 6.74(1H, brs),                       7.26-7.42(4H, m)                                                    879        0.91(3H, t, J=7.3), 1.33(2H, sextet, J=7.3), 1.56(2H, quintet,                 J=7.3),                                                                        2.31(3H, s), 2.40(2H, t, J=7.3), 2.81(3H, d, J=4.9), 3.36(3H,                  s), 5.10                                                                       (1H, s), 5.18(1H, d, J=12.2), 5.50(1H, d, J=12.2), 6.73(1H,                    brs), 7.26-                                                                    7.42(4H, m)                                                         882        134˜135° C.                                            883        1.18(6H, d, J=6.7), 1.95(3H, s), 2.27-2.36(2H, m), 2.83(3H, d,                 J=4.9),                                                                        3.34(3H, s), 3.45-3.49(2H, m), 3.59-3.67(2H, m), 5.00(1H, d,                   J=                                                                             12.2), 5.09(1H, s), 5.30(1H, d, J=12.2), 6.75(1H, brs),                        7.28-7.43(4H, m)                                                    891        0.88(3H, t, J=7.3), 1.18(6H, d, J=6.7), 1.26-1.44(4H, m),                      2.28-2.44                                                                      (4H, m), 2.83(3H, d, J=4.9), 3.33(3H, s), 3.42-3.46(2H, m),                    3.58-                                                                          3.64(2H, m), 4.98(1H, d, J=12.2), 5.09(1H, s), 5.29(1H, d,                     J=12.2),                                                                       6.75(1H, brs), 7.27-7.43(4H, m)                                     898        2.76(3H, d, J=4.9), 2.99(4H, t, J-4.3), 3.04(3H, s), 3.68(4H,                  t, J=4.3),                                                                     4.90(1H, s), 4.97(1H, d, J=12.2), 5.33(1H, d, J=12.2),                         6.61(1H, brs),                                                                 7.20-7.43(8H, m)                                                    904        2.34(3H, s), 2.70(3H, d, J=4.9), 3.01(4H, t, J=4.9), 3.04(3H,                  s), 3.67                                                                       (4H, t, J=4.9), 4.91(1H, s), 4.99(1H, d, J=12.2), 5.28(1H, d,                  J=12.2),                                                                       6.51(1H, brs), 7.15-7.36(8H, m)                                     905        1.12(6H, d, J=6.7), 2.29-2.39(2H, m), 2.35(3H, s), 2.69(3H, d,                 J=                                                                             4.9), 3.04(3H, s), 3.22-3.30(2H, m), 3.59-3.70(2H, m),                         4.90(1H, s),                                                                   4.98(1H, d, J=12.2), 5.26(1H, d, J=12.2), 6.50(1H, brs),                       7.14-7.39                                                                      (8H, m)                                                             906        130˜131° C.                                            907        1.13(6H, d, J=6.7), 2.32-2.42(2H, m), 2.77(3H, d, J=4.9),                      2.98(3H, s),                                                                   3.15-3.23(2H, m), 3.59-3.71(2H, m), 4.86(1H, s), 4.96(1H, d,                   J=12.2),                                                                       5.34(1H, d, J=12.2), 6.64(1H, brs), 7.25-7.28(4H, m), 7.47(2H,                 d,                                                                             J=7.9), 7.63(2H, d, J=7.9)                                          910        2.71(3H, d, J=4.9), 3.01(4H, t, J=4.9), 3.05(3H, s), 3.68(4H,                  t, J=4.9),                                                                     3.80(3H, s), 4.93(1H, s), 5.00(1H, d, J=12.2), 5.29(1H, d,                     J=12.2),                                                                       6.53(1H, brs), 6.87(2H, d, J=8.5), 7.23-7.39(6H, m)                 911        1.12(3H, d, J=6.7), 1.13(3H, d, J=6.7), 2.28-2.38(2H, m),                      2.70(3H, d                                                                     J=4.9), 3.06(3H, s), 3.22-3.27(2H, m), 3.56-3.70(2H, m),                       3.81(3H, s),                                                                   4.92(1H, s), 5.00(1H, d, J=12.2), 5.28(1H, d, J=12.2),                         6.52(1H, brs),                                                                 6.87(2H, d, J=9.2), 7.23-7.34(6H, m)                                941        2.21(3H, s), 2.36(3H, s), 2.85(3H, d, J=4.9), 3.36(3H, s),                     5.05(1H, s),                                                                   5.34(1H, d, J=12), 5.64(1H, d, J=12), 6.82(1H, brs),                           7.33-7.40(5H, m),                                                              7.48-7.50(1H, m), 7.81(2H, d, J=8.8)                                982        0.72-0.74(2H, m), 1.00-1.05(2H, m), 1.61(1H, m), 2.82(3H, d,                   J=4.9),                                                                        3.54(3H, s), 4.26-4.31(1H, m), 4.55-4.60(1H, m), 5.07(1H, s),                  6.85                                                                           (1H, brs), 6.84-6.88(2H, m), 7.30-7.41(6H, m)                       995        0.68-0.70(2H, m), 1.00-1.05(2H, m), 1.80-1.85(1H, m), 2.30(3H,                 s),                                                                            2.81(3H, d, J=4.9), 3.31(3H, s), 4.20(1H, d, J=13.0), 4.60(1H,                 d,                                                                             J=13.0), 5.09(1H, s), 6.60(1H, brs), 6.75(2H, m),                              7.00-7.20(2H, m),                                                              7.30-7.55(4H, m)                                                    1017       2.33(3H, s), 2.68(3H, d, J=4.9), 3.30(3H, s), 4.59(2H, s),                     4.67(1H,                                                                       d, J=12.0), 4.91(1H, d, J=12.0), 5.01(1H, s), 6.70(1H, brs),                   7.10-                                                                          7.20(2H, m), 7.29-7.41(6H, m)                                       1030       2.82(3H, d, J=4.9), 3.35(3H, s), 5.10(1H, s), 5.44(1H, d,                      J=12.8),                                                                       5.74(1H, d, J=12.8), 6.83(1H, brs), 7.30-7.58(7H, m), 8.07(2H,                 d,                                                                             J=7.9)                                                              __________________________________________________________________________

2-Oxo-2- 2-(tetrahydropyran-2-yloxymethyl)phenyl!-acetic acid derivatives were synthesized by the method in Reference Examples 1 to 3 described below.

Reference Example 1 Synthesis of 1-bromo-2-(tetrahydropyran-2-yloxy-methyl)benzene

Pyridinium p-toluenesulfonate (0.30 g) was added to a solution of 2-bromobenzylalcohol (25.00 g, 0.134 mol) in methylene chloride (100 ml), and the mixture was stirred at room temperature. 3,4-Dihydro-2H-pyran (16.86 g, 0.200 mol) was added thereto. The mixture was stirred at room temperature for 2 hours, and saturated aqueous sodium bicarbonate solution (200 ml) was added. The resulting mixture was extracted with methylene chloride and dried over anhydrous magnesium sulfate. Evaporation of the solvent gave the desired compound 1-bromo-2-(tetrahydropyran-2-yloxy-methyl)benzene (36.00 g, 99.3%) as an oil.

NMR (δ ppm, TMS/CDCl₃): 1.45-1.80(6H,m), 3.45-3.55 (1H,m), 3.80-3.90(1H,m), 4.52(1H,d,J=15.0), 4.80(1H,m), 4.90 (1H,d,J=15.0), 7.16(1H,t,J=7.3), 7.31(1H,t,J=7.3), 7.51 (1H,d,J=7.3), 7.54(1H,d,J=7.3).

Reference Example 2 Synthesis of ethyl 2-oxo-2- 2-(tetrahydropyran-2-yloxymethyl)phenyl!acetate

Magnesium (2.67 g, 0.110 mol) and bromoethane (0.20 ml) were added to a solution of 1-bromo-2-(tetrahydropyran-2-yloxymethyl)benzene (27.11 g, 0.100 mol) in tetrahydrofuran (50 ml) under an atmosphere of nitrogen, and the mixture was stirred at room temperature for 1 hour to prepare a Grignard reagent. The Grignard reagent was added dropwise to a solution of diethyl oxalate (29.23 g, 0.200 mol) in tetrahydrofuran (100 ml) cooled to -78° C. After stirring for 1 hour at -78° C., water (150 ml) was added. The mixture was extracted with ether, dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=4/1) to give the desired compound ethyl 2-oxo-2- 2-(tetrahydropyran-2-yloxymethyl)phenyl!acetate (22.60 g, 77.3%) as an oil.

NMR (δ ppm, TMS/CDCl₃): 1.38(3H,t,J=7.0), 1.40-1.85 (6H,m), 3.50-3.60(1H,m), 3.80-3.90(1H,m), 4.32-4.40(2H,m), 4.69(1H,m), 4.85(1H,d,J=14.6), 5.09(1H,d,J=14.6), 7.43 (1H,t,J=7.3), 7.58-7.70(3H,m).

Reference Example 3 Synthesis of 2-oxo-N-methyl-2- 2-(tetrahydropyran-2-yloxymethyl)phenyl!acetamide

40% monomethylamine--methanol (2.65 g, 34.1 mmol) solution was added to a solution of ethyl 2-oxo-2- 2-(tetra-hydropyran-2-yloxymethyl)phenyl!acetate (2.00 g, 6.8 mmol) in methanol (20 ml), and the mixture was stirred at room temperature for 2 hours. The solvent was evaporated, and the residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=4/1) to give the desired compound 2-oxo-N-methyl-2- 2-(tetrahydropyran-2-yloxymethyl)phenyl!-acetamide (1.30 g, 69%) as an oil.

NMR (δ ppm, TMS/CDCl₃): 1.56-1.80(6H,m), 2.96 (3H,d,J=5.5), 3.40-3.50(1H,m), 3.75-3.85(1H,m), 4.60(1H,m), 4.75(1H,d,J=14.0), 4.97(1H,d,J=14.0), 7.04(1H,brs), 7.35-7.39(1H,m), 7.51(2H,m), 7.79(1H,d,J=7.9).

The following pot experiments illustrate the controlling effects of foliage application of the various compounds of the present invention on various plant diseases.

Experimental Method

All the tests assessed controlling effects. That is, the tests were carrried out by spraying a liquid sample to a test plant and inoculating the plant with a pathogen 24 hours thereafter. A test compound was dissolved in a small amount of N,N-dimethylformamide, and the solution was diluted to 500 ppm with distilled water containing a spreader to prepare a liquid sample. The percent control was calculated according to the following equation:

Percent control (%)={(severity, number of lesions, etc. in untreated plot--severity, number of lesions, etc. in treated plot)/severity, number of lesions, etc. in untreated plot}×100

Test Example 1 Controlling effect on Pyricularia oryzae

Two-week rice seedlings (var.: AICHIASAHI) were transplanted in plastic cups (each 9 cm in diameter) and cultivated another 2 weeks. The test compound in the form of a solution or a suspension was sprayed to the foliage of the rice-seedlings. The inoculation of the pathogen was carried out by spraying to the foliage a conidia suspension of Pyricularia oryzae cultured in an oatmeal medium. After the inoculation, the test plant was kept in a moist chamber (28° C., 100% R.H.) for 24 hours and then in a greenhouse for 5 days. Six days after the inoculation, the number of lesions on the leaves of the inoculated plant was measured to calculate the percent control.

The compound showed high percent control to Pyricularia oryzae. For example, the following compounds showed a percent control of not less than 90% at 500 ppm: Compound Nos. 75, 139, 140, 161, 163, 165, 166, 170, 175, 176, 186, 193, 194, 196, 197, 211, 212, 214, 217, 219, 221, 223, 233, 267, 372, 423, 427, 429, 432, 448, 459, 465, 466, 467, 472, 474, 475, 476, 477, 486, 488, 491, 492, 494, 495, 499, 500, 501, 503, 513, 516, 517, 518, 526, 529, 532, 535, 544, 553, 556, 559, 562, 580, 609, 616, 639, 678, 680, 682, 684, 686, 688, 690, 692, 698, 701, 702, 704, 707, 710, 717, 718, 721, 722, 725, 726, 733, 736, 739, 740, 773, 781, 785, 813, 819, 824, 837, 883 and 982.

Test Example 2 Controlling effect on cucumber powdery mildew (Sphaerotheca fuliginea)

Seeds of cucumber (var.: TSUKUBASHIROIBO) were sown in plastic cups (each 9 cm in diameter), followed by cultivation for 2 to 3 weeks. The liquid test sample in the form of a solution or suspension was sprayed on the surface of their first leaves. The pathogen was inoculated by spraying to the leaves a conidia suspension of Sphaerotheca fuliginea which had been cultured on the cucumber leaves. After the inoculation, the plants were kept in a greenhouse at 20° C. Ten days after the inoculation, the infected area on the leaf was observed, and the percent control was calculated.

The compound showed high percent control to Sphaerotheca fuliginea. For example, the following compounds showed a percent control of not less than 97% at 500 ppm: Compound Nos. 64, 75, 78, 113, 139, 140, 141, 142, 143, 144, 145, 149, 151, 152, 155, 156, 161, 165, 170, 173, 174, 176, 179, 180, 183, 185, 186, 189, 193, 194, 195, 196, 197, 198, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 221, 223, 231, 233, 262, 263, 267, 291, 292, 296, 297, 362, 372, 417, 420, 423, 427, 429, 432, 433, 436, 437, 443, 448, 453, 454, 459, 461, 465, 466, 467, 468, 469, 472, 474, 475, 476, 477, 482, 486, 488, 489, 491, 492, 494, 497, 498, 500, 501, 503, 504, 506, 513, 515, 516, 517, 518, 520, 523, 526, 527, 529, 532, 535, 541, 542, 544, 553, 556, 559, 577, 580, 586, 587, 589, 590, 592, 593, 603, 606, 609, 616, 627, 639, 678, 680, 682, 684, 686, 688, 690, 692, 698, 701, 702, 704, 707, 710, 717, 718, 721, 722, 725, 726, 733, 734, 736, 737, 738, 739, 740, 756, 759, 773, 777, 781, 785, 813, 819, 824 and 883.

Test Example 3 Controlling effect on Pseudoperonospora cubensis

The seeds of cucumber (var.: TSUKUBASHIROIBO) were sown in plastic cups (each 9 cm in diameter), followed by cultivation for 2 to 3 weeks. The test compound in the form of a solution or suspension was sprayed to the surface of their first leaves, and a zoosporangia suspension of Pseudoperonospora cubensis cultured on cucumber leaves was dropped on the above leaf surfaces to inoculate the test plants with the pathogen. After the inoculation, the plants were kept in a moist chamber at 20° C. for 10 days. Then, the increased diameters of the lesions around the inoculated part were measured and the percent control was calculated.

The compound showed high percent control to Pseudoperonospora cubensis. For example, the following compounds showed a percent control of not less than 90% at 500 ppm: Compound Nos. 74, 113, 139, 140, 156, 161, 165, 170, 176, 186, 189, 193, 194, 196, 197, 206, 207, 209, 210, 212, 216, 217, 218, 219, 221, 223, 231, 233, 263, 267, 291, 362, 372, 417, 420, 423, 427, 429, 432, 433, 443, 448, 453, 459, 465, 466, 467, 468, 472, 474, 476, 477, 478, 482, 487, 488, 489, 491, 492, 494, 495, 496, 497, 498, 499, 500, 501, 503, 504, 505, 506, 507, 508, 509, 512,.513, 515, 516, 517, 518, 523, 526, 527, 529, 535, 541, 542, 544, 553, 556, 559, 562, 576, 580, 581, 583, 586, 587, 589, 590, 606, 609, 616, 627, 639, 678, 680, 682, 684, 686, 688, 690, 692; 698, 701, 702, 704, 707, 710, 717, 718, 721, 722, 725, 726, 733, 734, 735, 736, 737, 739, 740, 756, 757, 758, 759, 773, 777, 781, 785, 813, 819, 824, 837, 883, 982, 995, 1016, 1019, 1030, 1031, 1033 and 1034.

Test Example 4 Controlling effect on Erysiphe graminis f. sp. tritici

The seeds of wheat (var.: NORIN No. 61) were sown in plastic cups (each 9 cm in diameter), followed by cultivation for 2 to 3 weeks. The test compound in the form of a solution or suspension was sprayed to the seedlings, and conidia of Erysiphe graminis f. sp. tritici cultured on wheat leaves were dropped on the test plants to inoculate the plants with the pathogen. After the inoculation, the plants were kept in a greenhouse at 20° C. Ten days after the inoculation, the infected area on the leaf was observed, and the percent control was calculated.

The compound showed high percent control to Erysiphe graminis f. sp. tritici. For example, the following compounds showed a percent control of not less than 90% at 500 ppm; Compound Nos. 2, 75, 113, 139, 140, 141, 142, 143, 144, 145, 151, 152, 161, 170, 174, .175, 176, 179, 184, 185, 186, 188, 189, 193, 194, 195, 196, 197, 198, 206, 212, 216, 217, 218, 219, 223, 263, 297, 362, 372, 417, 420, 423, 427, 429, 432, 433, 443, 448, 454, 459, 465, 466, 467, 474, 477, 488, 492, 498, 500, 517, 518, 526, 527, 541, 542, 590, 603, 627, 686, 701, 726, 739 and 883.

As described above, the present invention provides a novel α-substituted phenylacetic acid derivative having fungicidal activity, a process for producing it, intermediates for the process, and an agricultural fungicide containing it as an active ingredient. 

We claim:
 1. A compound of the formula (1): ##STR234## wherein R¹ is a halogen atom, hydroxyl, optionally substituted alkoxy, or amino optionally substituted by alkyl; Q is optionally substituted aryl; X is a hydrogen atom, halogen atom, optionally substituted alkyl, hydroxyl or optionally substituted alkoxy; Y is hydroxyl, alkylthio, optionally substituted alkoxy or optionally substituted amino, provided that, when R¹ is hydroxyl, Y is not alkoxy; Z is an oxygen atom or sulfur atom; M is an oxygen atom, or a sulfur atom; and n is 0 or 1; or a salt thereof.
 2. A compound according to claim 1, wherein R¹ is a halogen atom, hydroxyl, alkoxy, haloalkoxy, alkoxyalkoxy, or amino optionally substituted by alkyl, or a salt thereof.
 3. A compound according to claim 1, wherein R¹ is alkoxy, or a salt thereof.
 4. A compound according to claim 1, wherein R¹ is methoxy, or a salt thereof.
 5. A compound according to claim 1, wherein Q is a group of the formula (XX): ##STR235## wherein U, V and W are independently the same or different and are a hydrogen atom, halogen atom, optionally substituted alkyl, optionally substituted hydroxyl, alkylthio or optionally substituted amino, or a salt thereof.
 6. A compound according to claim 5, wherein U, V and W are the same or different and are a hydrogen atom, chlorine atom, methyl, trifluoromethyl or methoxy, or a salt thereof.
 7. A compound according to claim 1, wherein X is a hydrogen atom, or a salt thereof.
 8. A compound according to claim 1, wherein Y is alkoxy or a salt thereof.
 9. A compound according to claim 1, wherein Y is methoxy or a salt thereof.
 10. A compound according to claim 1, wherein Y is monoalkylamino, or a salt thereof.
 11. A compound according to claim 1, wherein Y is monomethylamino, or a salt thereof.
 12. A compound according to claim 1, wherein Z is an oxygen atom, or a salt thereof.
 13. A compound according to claim 1, wherein n is 0, or a salt thereof.
 14. A compound according to claim 1, wherein n is 1, or a salt thereof.
 15. A compound according to claim 1, wherein X is a hydrogen atom, R¹ is hydroxyl, Z is an oxygen atom, Y is amino optionally substituted by alkyl, M is an oxygen atom, Q is optionally substituted phenyl, and n is 0 or 1, or a salt thereof.
 16. A compound according to claim 1, wherein X is a hydrogen atom, R¹ is alkoxy, Z is an oxygen atom, Y is alkoxy or optionally substituted amino, M is an oxygen atom, Q is optionally substituted phenyl, and n is 0 or 1, or a salt thereof.
 17. A compound according to claim 1, whereinX is a hydrogen atom, R¹ is hydroxyl, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is phenyl, and n is 0; X is a hydrogen atom, R¹ is hydroxyl, Z is an oxygen atom, Y is amino, M is an oxygen atom, Q is phenyl, and n is 0; X is a hydrogen atom, R¹ is hydroxyl, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is 3,4-dimethylphenyl, and n is 0; X is a hydrogen atom, R¹ is hydroxyl, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is 3,5-dimethylphenyl, and n is 0; X is a hydrogen atom, R¹ is hydroxyl, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is 2-methylphenyl, and n is 1; X is a hydrogen atom, R¹ is hydroxyl, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is 2,5-dimethylphenyl, and n is 1; X is a hydrogen atom, R¹ is hydroxyl, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is 4-chloro-2-methylphenyl, and n is 1; X is a hydrogen atom, R¹ is methoxy, Z is an oxygen atom, Y is methoxy, M is an oxygen atom, Q is 2,5-dimethylphenyl, and n is 1; X is a hydrogen atom, R¹ is methoxy, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is 2,5-dimethylphenyl, and n is 1; X is a hydrogen atom, R¹ is methoxy, Z is an oxygen atom, Y is monomethylamino, M is an oxygen atom, Q is 4-chloro-2-methylphenyl, and n is 1; X is a hydrogen atom, R¹ is methoxy, Z is an oxygen atom; Y is monomethylamino, M is an oxygen atom, Q is 2-methylphenyl, and n is
 1. 18. An agricultural fungicidal composition comprising a compound according to claim 1 as an active ingredient.
 19. A process for producing a compound of the formula (I): ##STR236## wherein each symbol is as defined in claim 1, which comprises reacting a compound of the formula (XVIII): ##STR237## wherein D is a halogen atom, and the other symbols are as defined in claim 1, with a compound of the formula (XIX):

    Q--MH                                                      (XIX)

wherein each symbol is as defined in claim
 1. 20. A method for controlling phytopathogenic fungi which comprises applying a fungicidally effective amount of a compound according to claim 1 or a salt thereof as an active ingredient to a locus where phytopathogenic fungi propagate or will propagate.
 21. An agricultural fungicide comprising a fungicidally effective amount of the compound according to claim 1 and an agriculturally acceptable carrier. 